Academic literature on the topic 'Facteur de transcription ATF-6'
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Journal articles on the topic "Facteur de transcription ATF-6"
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FAWCETT, Timothy W., Jennifer L. MARTINDALE, Kathryn Z. GUYTON, Tsonwin HAI, and Nikki J. HOLBROOK. "Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein (C/EBP)–ATF composite site to regulate Gadd153 expression during the stress response." Biochemical Journal 339, no. 1 (March 25, 1999): 135–41. http://dx.doi.org/10.1042/bj3390135.
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Gadd153, also known as chop, encodes a member of the CCAAT/enhancer-binding protein (C/EBP) transcription factor family and is transcriptionally activated by cellular stress signals. We recently demonstrated that arsenite treatment of rat pheochromocytoma PC12 cells results in the biphasic induction of Gadd153 mRNA expression, controlled in part through binding of C/EBPβ and two uncharacterized protein complexes to the C/EBP–ATF (activating transcription factor) composite site in the Gadd153 promoter. In this report, we identified components of these additional complexes as two ATF/CREB (cAMP-responsive-element-binding protein) transcription factors having differential binding activities dependent upon the time of arsenite exposure. During arsenite treatment of PC12 cells, we observed enhanced binding of ATF4 to the C/EBP–ATF site at 2 h as Gadd153 mRNA levels increased, and enhanced binding of ATF3 complexes at 6 h as Gadd153 expression declined. We further demonstrated that ATF4 activates, while ATF3 represses, Gadd153 promoter activity through the C/EBP–ATF site. ATF3 also repressed ATF4-mediated transactivation and arsenite-induced activation of the Gadd153 promoter. Our results suggest that numerous members of the ATF/CREB family are involved in the cellular stress response, and that regulation of stress-induced biphasic Gadd153 expression in PC12 cells involves the ordered, sequential binding of multiple transcription factor complexes to the C/EBP–ATF composite site.
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Mori, Kazutoshi. "Divest Yourself of a Preconceived Idea: Transcription Factor ATF6 Is Not a Soluble Protein!" Molecular Biology of the Cell 21, no. 9 (May 2010): 1435–38. http://dx.doi.org/10.1091/mbc.e09-07-0600.
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The unfolded protein response (UPR), an evolutionarily conserved transcriptional induction program that is coupled with intracellular signaling from the endoplasmic reticulum (ER) to the nucleus, is activated to cope with ER stress and to maintain the homeostasis of the ER. In 1996, we isolated a basic leucine zipper protein, which had been previously named activating transcription factor (ATF)6, as a candidate transcription factor responsible for the mammalian UPR. Subsequent analysis, however, was confounding. The problem was eventually tracked down to an unusual property of ATF6: rather than being a soluble nuclear protein, as expected for an active transcription factor, ATF6 was instead synthesized as a transmembrane protein embedded in the ER, which was activated by ER stress-induced proteolysis. ATF6 was thus unique: an ER stress sensor/transducer that is involved in all steps of the UPR, from the sensing step in the ER to the transcriptional activation step in the nucleus.
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Keeton, Adam B., Katherine D. Bortoff, J. Lee Franklin, and Joseph L. Messina. "Blockade of Rapid Versus Prolonged Extracellularly Regulated Kinase 1/2 Activation Has Differential Effects on Insulin-Induced Gene Expression." Endocrinology 146, no. 6 (June 1, 2005): 2716–25. http://dx.doi.org/10.1210/en.2004-1662.
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Abstract In the present work, insulin’s regulation of expression of activating transcription factor 3 (ATF-3), the putative transcription factor proline-rich induced protein (Pip)92, and insulin-inducible gene-1 (Insig-1) (an ER resident protein involved in regulation of sterol-responsive element-binding protein 1 activation) have been examined in a liver-derived cell line (rat H4IIE hepatoma cells). We report that: 1) insulin-induced transcription of ATF-3, Pip92, and Insig-1 required MEK-ERK activation; 2) insulin-induced transcription of ATF-3 and Pip92 reached maximum levels within 15 min and was blocked by wortmannin but not LY294002; 3) in contrast, the maximum level of insulin-induced transcription of Insig-1 was delayed and was not blocked by either wortmannin or LY294002; 4) insulin activated ERK1/2 in two distinct phases, a rapid peak and a later plateau; 5) the delayed plateau phase of insulin-induced ERK1/2 activation was partially phosphatidylinositol 3-OH-kinase dependent; and 6) however, the rapid, insulin-induced peak of ERK1/2 activation was blocked by wortmannin but not LY294002.
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Seo, Hye-Young, Yong Deuk Kim, Kyeong-Min Lee, Ae-Kyung Min, Mi-Kyung Kim, Hye-Soon Kim, Kyu-Chang Won, et al. "Endoplasmic Reticulum Stress-Induced Activation of Activating Transcription Factor 6 Decreases Insulin Gene Expression via Up-Regulation of Orphan Nuclear Receptor Small Heterodimer Partner." Endocrinology 149, no. 8 (May 1, 2008): 3832–41. http://dx.doi.org/10.1210/en.2008-0015.
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The highly developed endoplasmic reticulum (ER) structure of pancreatic β-cells is a key factor in β-cell function. Here we examined whether ER stress-induced activation of activating transcription factor (ATF)-6 impairs insulin gene expression via up-regulation of the orphan nuclear receptor small heterodimer partner (SHP; NR0B2), which has been shown to play a role in β-cell dysfunction. We examined whether ER stress decreases insulin gene expression, and this process is mediated by ATF6. A small interfering RNA that targeted SHP was used to determine whether the effect of ATF6 on insulin gene expression is mediated by SHP. We also measured the expression level of ATF6 in pancreatic islets in Otsuka Long Evans Tokushima Fatty rats, a rodent model of type 2 diabetes. High glucose concentration (30 mmol/liter glucose) increased ER stress in INS-1 cells. ER stress induced by tunicamycin, thapsigargin, or dithiotreitol decreased insulin gene transcription. ATF6 inhibited insulin promoter activity, whereas X-box binding protein-1 and ATF4 did not. Adenovirus-mediated overexpression of active form of ATF6 in INS-1 cells impaired insulin gene expression and secretion. ATF6 also down-regulated pancreatic duodenal homeobox factor-1 and RIPE3b1/MafA gene expression and repressed the cooperative action of pancreatic duodenal homeobox factor-1, RIPE3b1/MafA, and β-cell E box transactivator 2 in stimulating insulin transcription. The ATF6-induced suppression of insulin gene expression was associated with up-regulation of SHP gene expression. Finally, we found that expression of ATF6 was increased in the pancreatic islets of diabetic Otsuka Long Evans Tokushima Fatty rats, compared with their lean, nondiabetic counterparts, Long-Evans Tokushima Otsuka rats. Collectively, this study shows that ER stress-induced activation of ATF6 plays an important role in the development of β-cell dysfunction.
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Spinello, Zaira, Luana Abballe, Elena Splendiani, Angela Di Giannatale, Felice Giangaspero, Angela Mastronuzzi, Elisabetta Ferretti, Evelina Miele, and Giuseppina Catanzaro. "MEDB-09. Unraveling the role of unfolded protein response in medulloblastoma cancer stem cells." Neuro-Oncology 24, Supplement_1 (June 1, 2022): i105—i106. http://dx.doi.org/10.1093/neuonc/noac079.384.
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Abstract Medulloblastoma (MB) is the most common malignant childhood brain tumor. The current clinical approach consists of multimodal strategies with debilitating long-term effects and risk of tumor recurrence. Medulloblastoma stem cells (MBSCs) are a fraction of tumor cells with high proliferation potential and the capability to adapt to adverse/restrictive conditions in tumor milieu thus driving the refractoriness to conventional therapies. Recently, high basal levels of Unfolded Protein Response (UPR) molecules have been found in tumors of different tissue-origin and are correlated with poor prognosis and low patient survival. However, little is known about the role of UPR in MB. We investigated the expression and activation of UPR players in MBSCs. Human group 3 MB (G3MB) cell lines, specifically CHLA-01, D283- and D341-Med, were grown in Vitamin A and/or FBS or in stem selective medium (B27™) for 72 h before collection. Cells were fixed, stained with proper primary antibodies and images were acquired by confocal microscopy. The analysis of the transcription factors ATF-4 and CHOP revealed their elevated nuclear expression and co-localization, which resulted to be more marked in G3MB stem-like cells than in the differentiated ones. Also the ATF-6 branch was investigated, in differentiating conditions D283 and D341-Med showed a greater activation of ATF-6, represented by its nuclear localization, in respect to stem cells, while CHLA-01 did not show differences. Conversely XBP1, the transcription factor downstream IRE1 signaling, was not expressed in the three cell lines. Lastly, a Kaplan-Meier analysis on MB patients showed a worse prognosis with a shorter survival rate of patients expressing high ATF4 transcript levels. Our results reveal, even in resting conditions, preferential activation of the PERK branch in G3MB cells grown in stem-like condition suggesting that ATF-4 might be a promising therapeutic and prognostic factor to specifically target the stem compartment in aggressive MB.
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Fu, Lingchen, and Michael S. Kilberg. "Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response." Physiological Genomics 45, no. 4 (February 15, 2013): 127–37. http://dx.doi.org/10.1152/physiolgenomics.00160.2012.
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Mammalian cells respond to amino acid deprivation through multiple signaling pathways referred to as the amino acid response (AAR). Transcription factors mediate the AAR after their activation by several mechanisms; examples include translational control (activating transcription factor 4, ATF4), phosphorylation (p-cJUN), and transcriptional control (ATF3). ATF4 induces ATF3 transcription through a promoter-localized C/EBP-ATF response element (CARE). The present report characterizes an ATF/CRE site upstream of the CARE that also contributes to AAR-induced ATF3 transcription. ATF4 binds to the ATF/CRE and CARE sequences and both are required for a maximal response to ATF4 induction. ATF3, which antagonizes ATF4 and represses its own gene, also exhibited binding activity to the ATF/CRE and CARE sequences. The AAR resulted in elevated total cJUN and p-cJUN protein levels and both forms exhibited binding activity to the ATF/CRE and CARE ATF3 sequences. Knockdown of AAR-enhanced cJUN expression blocked induction of the ATF3 gene and mutation of either the ATF/CRE or the CARE site prevented the cJUN-dependent increase in ATF3-driven luciferase activity. The results indicate that both increased cJUN and the cis-acting ATF/CRE sequence within the ATF3 promoter contribute to the transcriptional activation of the gene during the AAR.
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Vidičević-Novaković, Sašenka, and Željka Stanojević. "Molecular mechanisms involved in endoplasmic reticulum stress development: What do we know today." Medicinski podmladak 75, no. 2 (2024): 36–42. http://dx.doi.org/10.5937/mp75-44722.
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Endoplasmic reticulum (ER) is an intracellular organelle involved in protein synthesis and folding. When the balance between cell needs for proteins and ER capacity to fold proteins is disrupted, nonfunctional, unfolded, or misfolded proteins accumulate in ER lumen, leading to endoplasmic reticulum stress (ER stress). One of the ways cell uses to overcome ER stress is unfolded protein response (UPR) activation. UPR is initiated by the activation of three ER transmembrane proteins. These proteins are IRE-1a (inositol requiring enzyme-1a), PERK (protein kinase RNA-like endoplasmic reticulum kinase) and ATF6 (activating transcription factor 6) and they are activated when ER chaperone, GRP78 (glucose-regulates protein 78) releases their intraluminal domains. Activation of these transmembrane sensors starts mechanisms that should restore ER function. If ER function is not restored and balance is not achieved, apoptosis is induced in order to maintain cell homeostasis. Activated IRE-1a leads to XBP-1 (X-box binding protein-1) mRNA splicing and activates MAP kinases and inflam-matory pathways that involve nuclear factor cB (NFcB). Activated ATF 6 (ATF6f) functions as a transcriptional factor and increases gene expression for XBP-1, while PERK activation leads to phosphorylation and inactivation of eukaryotic initiation factor 2 (eIF2a) which further leads to decreased protein synthesis. Additionally, eIF2a phosphorylation leads to selective synthesis of ATF4, a transcriptional factor that in irreversibly damaged cells induces cell death activation by C/EBP homologous protein (CHOP) transcription. It is known that ER stress and UPR have a role in different diseases pathogenesis such as diabetes, inflammation, tumors and neurodegenerative diseases. Knowing signaling pathways of UPR and mechanisms by which UPR is involved in diseases pathogenesis can be very significant in targeted therapeutic approaches development.
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Ross, Heather L., Michael R. Nonnemacher, Tricia H. Hogan, Shane J. Quiterio, Andrew Henderson, John J. McAllister, Fred C. Krebs, and Brian Wigdahl. "Interaction between CCAAT/Enhancer Binding Protein and Cyclic AMP Response Element Binding Protein 1 Regulates Human Immunodeficiency Virus Type 1 Transcription in Cells of the Monocyte/Macrophage Lineage." Journal of Virology 75, no. 4 (February 15, 2001): 1842–56. http://dx.doi.org/10.1128/jvi.75.4.1842-1856.2001.
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ABSTRACT Recent observations have shown two CCAAT/enhancer binding protein (C/EBP) binding sites to be critically important for efficient human immunodeficiency virus type 1 (HIV-1) replication within cells of the monocyte/macrophage lineage, a cell type likely involved in transport of the virus to the brain. Additionally, sequence variation at C/EBP site I, which lies immediately upstream of the distal nuclear factor kappa B site and immediately downstream of a binding site for activating transcription factor (ATF)/cyclic AMP response element binding protein (CREB), has been shown to affect HIV-1 long terminal repeat (LTR) activity. Given that C/EBP proteins have been shown to interact with many other transcription factors including members of the ATF/CREB family, we proceeded to determine whether an adjacent ATF/CREB binding site could affect C/EBP protein binding to C/EBP site I. Electrophoretic mobility shift analyses indicated that selected ATF/CREB site variants assisted in the recruitment of C/EBP proteins to an adjacent, naturally occurring, low-affinity C/EBP site. This biophysical interaction appears to occur via at least two mechanisms. First, low amounts of CREB-1 and C/EBP appear to heterodimerize and bind to a site consisting of a half site from both the ATF/CREB and C/EBP binding sites. In addition, CREB-1 homodimers bind to the ATF/CREB site and recruit C/EBP dimers to their cognate weak binding sites. This interaction is reciprocal, since C/EBP dimer binding to a strong C/EBP site leads to enhanced CREB-1 recruitment to ATF/CREB sites that are weakly bound by CREB. Sequence variation at both C/EBP and ATF/CREB sites affects the molecular interactions involved in mediating both of these mechanisms. Most importantly, sequence variation at the ATF/CREB binding site affected basal LTR activity as well as LTR function following interleukin-6 stimulation, a treatment that leads to increases in C/EBP activation. Thus, HIV-1 LTR ATF/CREB binding site sequence variation may modulate cellular signaling at the viral promoter through the C/EBP pathway.
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Xu, Linhao, Yanli Bi, Yizhou Xu, Yihao Wu, Xiaoxue Du, Yixuan Mou, and Jian Chen. "Suppression of CHOP Reduces Neuronal Apoptosis and Rescues Cognitive Impairment Induced by Intermittent Hypoxia by Inhibiting Bax and Bak Activation." Neural Plasticity 2021 (August 21, 2021): 1–14. http://dx.doi.org/10.1155/2021/4090441.
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Our previous study showed that growth arrest- and DNA damage-inducible gene 153 (GAD153/CHOP) plays an important role in intermittent hypoxia- (IH-) induced apoptosis and impaired synaptic plasticity. This study is aimed at determining which signaling pathway is activated to induce CHOP and the role of this protein in mitochondria-dependent apoptosis induced by IH. In the in vivo study, mice were placed in IH chambers for 8 h daily over a period of 2 weeks; the IH chambers had oxygen (O2) concentrations that oscillated between 10% and 21%, cycling every 90 s. In the in vitro study, PC12 cells were exposed to 21% O2 (normoxia) or 8 IH cycles (25 min at 21% O2 and 35 min at 0.1% O2 for each cycle). After 2 weeks of IH treatment, we observed that the expression levels of phosphorylated protein kinase-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 4 (ATF-4) and phosphorylated eukaryotic initiation factor 2 alpha (p-elf2α), were increased, but the levels of activating transcription factor 6 (ATF-6) and inositol-requiring enzyme 1 (IRE-1) were not increased. GSK2606414, a specific chemical inhibitor of the PERK pathway, reduced the expression of p-PERK, ATF-4, p-elf2α, and CHOP and rescued ER structure. In addition, Bax and Bak accumulated in the mitochondria after IH treatment, which induced cytochrome c release and initiated apoptosis. These effects were prevented by GSK2606414 and CHOP shRNA. Finally, the impaired long-term potentiation and long-term spatial memory in the IH group were rescued by GSK2606414. Together, the data from the in vitro and in vivo experiments indicate that IH-induced apoptosis and impaired synaptic plasticity were mediated by the PERK-ATF-4-CHOP pathway. Suppressing PERK-ATF-4-CHOP signaling pathway attenuated mitochondria-dependent apoptosis by reducing the expression of Bax and Bak in mitochondria, which may serve as novel adjunct therapeutic strategy for ameliorating obstructive sleep apnea- (OSA-) induced neurocognitive impairment.
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Konsavage, Wesley M., Lianqin Zhang, Yuchieh Wu, and Jeffrey S. Shenberger. "Hyperoxia-induced activation of the integrated stress response in the newborn rat lung." American Journal of Physiology-Lung Cellular and Molecular Physiology 302, no. 1 (January 1, 2012): L27—L35. http://dx.doi.org/10.1152/ajplung.00174.2011.
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Diverse environmental stresses stimulate eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, leading to a stress-resistant state characterized by global attenuation of protein synthesis and induction of cytoprotective genes. The signal transduction network culminating in these effects is referred to as the integrated stress response (ISR) or, when initiated by misfolded proteins within the endoplasmic reticulum (ER), the unfolded protein response (UPR). Given that we previously reported that exposure of 4-day-old Sprague-Dawley rats to 95% O2 (Ox) diminishes global pulmonary protein synthesis and increases eIF2α phosphorylation, we conducted the current study to determine whether Ox activates the ISR or UPR. We found that Ox-induced alterations in ER morphology of alveolar type II cells and interstitial fibroblasts were not associated with activation of the UPR sensors PERK or activating transcription factor (ATF) 6 or with X-box binding protein-1 mRNA splicing in whole lung extracts. Exposure to Ox enhanced ATF4 immunoreactivity and nuclear protein content, followed by a 2- and 5-fold increase in ATF3 protein and mRNA expression, respectively. The accumulation of nuclear ATF4 protein coincided with induction of glutamate-cysteine ligase catalytic subunit, an ISR-responsive gene. Immunohistochemistry revealed that changes in ATF3/4 expression were prominent in the alveolus, whereas primary cell culture implicated epithelial and endothelial cells as targets. Finally, induction of ISR intermediates in the intact lung occurred in the absence of the phosphorylation of PKR, JNK, ERK1/2, and p38 MAPK. These findings demonstrate that Ox activates the ISR within the newborn lung and highlight regional and cell-specific alterations in the expression ISR transcription factors that regulate redox balance.
Dissertations / Theses on the topic "Facteur de transcription ATF-6"
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Goetz, Jean. "Etude structurale et fonctionnelle d'un facteur de transcription de la famille atf/creb." Université Louis Pasteur (Strasbourg) (1971-2008), 1996. http://www.theses.fr/1996STR13177.
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Un adnc codant pour trois isoformes (atfa1, a2 et a3) d'un facteur de transcription de la famille atf/creb a ete isole dans notre laboratoire. Nous avons montre que les proteines atfa relaient la transactivation par l'oncoproteine e1a 289r de l'adenovirus et que le domaine a zinc d'atfa est essentiel a cette activite. Une interaction directe avec e1a, impliquant des regions situees respectivement du cote amino et carboxy-terminal de la proteine atfa, a ete revelee par des experiences in vitro. Les proteines atfa se lient a l'adn sous forme d'homodimeres par l'intermediaire de leur region basique-glissiere a leucines (blz). Elles peuvent egalement former des heteodimeres avec des membres de la famille jun/fos, ce qui modifie leur specificite de liaison a l'adn et stimule leur activite transcriptionnelle. Les proteines atfa sont localisees dans le noyau de la cellule et un signal de localisation nucleaire bi-partite englobant la region basique du domaine blz a ete cartographie. Une activite proteine kinase, fortement associee a la region amino-terminale (1-82) de atfa, a ete detectee et identifiee a jnk2 par ses proprietes immunologiques et son profil d'induction. Le gene humain codant pour atfa, localise sur le chromosome 12 (q12-q14): il possede une structure multi-exonique, caracterisee par des sites donneurs alternatifs d'epissage responsables de la synthese des differentes isoformes. Une sequence de 200 pb en amont des sites d'initiation de la transcription, riche en nucleotides g et c et depourvue de boites tata ou caat, constitue un promoteur minimal et comporte plusieurs sites potentiels de liaison pour des facteurs de transcription situes dans des regions protegees contre l'action de la dnase i. Nous avons demontre par hybridation in situ, que l'expression du gene atfa est ubiquitaire mais faible au cours de l'embryogenese et chez la souris adulte. Certains tissus, comme les epithelia, le myocarde et certaines cellules du systeme nerveux central, presentent cependant une expression significativement accrue
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BAHR, ANNE. "Caracterisation et etudes fonctionnelles de plusieurs proteines associees au facteur de transcription atf-a." Université Louis Pasteur (Strasbourg) (1971-2008), 1998. http://www.theses.fr/1998STR13110.
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Le gene humain atf-a code au moins pour cinq isoformes d'une famille de facteurs de transcription (nommes atf-a0 a atf-a4). Dans le but de caracteriser la fonction de ces proteines, nous avons entrepris une serie d'experiences visant a identifier les partenaires de ces facteurs. Nous avons montre, en utilisant des techniques d'immunoprecipitation, que la proteine atf-a etait un partenaire privilegie des proteines c-jun et c-fos (les composants du facteur de transcription ap-1). Nous avons egalement demontre que jnk2 (une proteine kinase activant la proteine c-jun en la phosphorylant) interagissait avec atf-a in vivo. Ces resultats suggerent qu'une des fonctions des facteurs atf-a serait d'apporter la kinase jnk2 a proximite de ses cibles (telles que c-jun) en formant des heterodimeres avec ces dernieres. D'autre part, lors du criblage d'une banque d'adnc par la technique du double-hybride, nous avons identifie plusieurs autres partenaires d'atf-a parmi lesquels nous avons caracterise une nouvelle proteine kinase (mpky), une nouvelle proteine dont la fonction est completement inconnue (maif) et une proteine (mblm) dont l'homologue humain est implique dans une maladie genetique rare, le syndrome de bloom. Cette derniere est un membre de la famille des proteines recq, une famille conservee des bacteries a l'homme et impliquee dans la recombinaison de l'adn. Nous avons demontre d'une part que la proteine mblm possede les activites helicase et atpase. Nous avons demontre ensuite que les mutations ponctuelles presentes chez des patients atteints par ce syndrome ont pour consequence d'affecter simultanement les deux activites enzymatiques des proteines mutantes, mais aussi de perturber l'entree de ces proteines dans le noyau. Ces resultats suggerent que la structure tri-dimentionnelle des proteines mutantes testees est fortement perturbee.
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Tardif, Derek. "Implication du facteur de transcription GATA-6 dans la régénération musculaire." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112311.
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Efficient muscle regeneration is essential in mammals in order to overcome daily stress such as wounds, exercise and pathologic processes. This regeneration relies on muscle stem cells, the satellite cells. After a lesion, satellite cells are activated, proliferate and differentiate in fonctionnal muscle fibers. Our laboratory has previously shown that the transcription factor GATA-6 is expressed in the satellite cells. The present thesis confirms the expression of this factor in this cell type. Also, it seems that GATA-6 could be implicated in the maintaining of quiescence of these cells. The GATA-6 heterozygous mouse muscle is characterized by an increase level of Myf5 and Pax7+ cells. Moreover, suppression of one copy of the GATA-6 gene in a muscular dystrophy model mouse, the mdx mice, alleviates its phenotype. Further experiments on a muscle-specific GATA-6 null mouse will allow a better understanding of the role of GATA-6 in muscle regeneration.Keywords. GATA-6, muscle regeneration, mdx, satellite cells
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Journiac, Nathalie. "Etude du rôle du facteur de transcription RORα dans la réaction gliale." Paris 6, 2007. http://www.theses.fr/2007PA066031.
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Notre objectif était de déterminer le rôle de RORalpha dans l’activation des astrocytes associée à une neurodégénérescence. Nous avons utilisé la souris staggerer exprimant une mutation perte de fonction dans le gène Rora à l’origine de la dégénérescence des neurones cérébelleux et réalisé des transfections stables de lignées astrocytaires. Nous avons montré que RORalpha, jusqu’alors considéré comme exclusivement neuronal, est exprimé dans les astrocytes et démontré qu’il module : -l’expression de la GFAP, un marqueur spécifique de l’activation astrocytaire. -la prolifération, avec un effet différent des isoformes RORalpha1 et 4. -la synthèse d’IL-6, un facteur clef de la réaction gliale, de façon ambivalente et en compétition avec Rev-erb, un autre facteur de transcription. L’étude de souris mutantes RORAsg/sg-p5’GFAP-LacZ confirme une anomalie de la fonction astroctaire. RORalpha est donc impliqué dans la modulation des mécanismes cellulaires et moléculaires de la réaction gliale.
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GAIRE, MIREILLE. "Etude d'un facteur de transcription implique dans l'expression des genes precoces de l'adenovirus : le facteur atf-a. purification, clonage et expression des sequences codantes." Strasbourg 1, 1990. http://www.theses.fr/1990STR13214.
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Le gene eiiae d'adenovirus, exprime pendant la phase precoce de l'infection sous le controle des proteines eia virales, est un excellent systeme-modele pour l'etude des mecanismes impliques dans la regulation de l'initiation de la transcription des genes transcrits par l'arn polymerase b. Durant ces dernieres annees la structure detaillee de ce promoteur a ete etablie. Il existe en amont de la tata box atypique plusieurs elements promoteurs, deux sites e2f et un site atf, qui sont essentiels a la fois pour la transcription basale et la transactivation du gene par eia. Nous avons cible notre etude sur l'element promoteur atf qui est egalement retrouve dans d'autres promoteurs precoces de l'adenovirus, eia, eiii, eiv, et dans les promoteurs de certains genes cellulaires. Nous avons purifie jusqu'a homogeneite le facteur de transcription qui se fixe sur cet element atf, a partir de cellules hela. Ce facteur correspond a une phosphoproteine de 40 kd et est capable de stimuler la transcription a partir du promoteur eiiae dans un systeme reconstitue in vitro. Nous avons ensuite clone la sequence codante du facteur atf en criblant une banque d'expression lambda gt11 d'adnc, a l'aide d'une sonde oligonucleotidique correspondant au site de liaison de ce facteur a l'adn. Trois especes d'adnc ont ete isolees codant pour les proteines atf-a+, atf-a, atf-a, qui ne different successivement que par l'absence d'un peptide de 11 et 21 acides amines dans la region nh#2-terminale. Les deux proteines atf-a et -a, les plus etudiees, reconnaissent le site atf/cre sous forme de dimere. Elles sont capables de former des heterodimeres avec la proteine c-jun. Dans des experiences de transfection, les trois proteines atf-a induisent la transcription d'un gene reporter a partir des sites atf de differents genes. Cependant, elles sont incapables de stimuler la transcription du promoteur eiiae en l'absence de la pro
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Pradeau, Karine. "Réactivation de l'herpèsvirus humain de type 6 (HHV-6) : outils de détection et mécanismes moléculaires." Limoges, 2005. http://www.theses.fr/2005LIMO0027.
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L'herpèsvirus humain de type 6 (HHV-6) est un virus très répandu qui reste dans l'organisme sous une forme latente après la primo-infection. Cette latence virale est entrecoupée d'épisodes de réactivation, s'accompagnant d'une production de nombreuses particules infectieuses. La réactivation semble anodine chez le sujet sain, mais peut être très grave dans différents contextes d'immunodépression, notamment après transplantation, A l'heure actuelle, les mécanismes permettant le maintien de la latence ou à l'inverse ceux entraînant la réactivation sont inconnus. L'objectif de ce travail de thèse était double. Dans un premier temps, des outils moléculaires permettant la détection de la multiplication d'HHV-6 ont été développés. Pour cela une technique de quantification par PCR en temps réel a été mise au point. De même la détection des ARNm du virus associés à sa réplication par une RT-PCR a été réalisée. Afin de tester ces outils de détection dans un contexte de réactivation, elles ont été appliquées à des prélèvements sanguins de patients transplantés. Les deux méthodes se sont alors révélées efficace pour mettre en évidence la réactivation d'HHV-6. Puis dans un deuxième temps, l'effet de l'expression du facteur de transcription NF-κB sur la transcription des gènes très précoces du virus a été recherché. Pour cela, un super-répresseur de NF-κB (IκBαMut) a été transfecté dans des cellules favorables à la croissance virale. En inhibant la voie canique de signalisation de NF-κB, une diminution de la réplication du virus, mise en évidence par une baisse de la transcription des ARNm viraux à l'aide d'une technique de RT-PCR quantitative et par une réduction du nombre de cellules en immunofluorescence, a été observée. Un rôle important du facteur de transcription NF-κB dans la multiplication du virus HHV-6 a ainsi été démontréHuman herpesvirus 6 (HHV-6) is a widespread virus that remains for life in a latent state after primary infection. But HHV-6 may reactivate, producing many infectious particles. This reactivation seems harmless in healthy subject, but can be very serious in various contexts of immunosuppression, such as organ transplant recipients. Actually, the mechanisms allowing the maintenance of latency or contrary those involving the reactivation are unknown. The objective of this work was double. In the fist time, molecular methods to detect HHV-6 multiplication were developed: a real time quantitative PCR method and a RT-PCR assay allowing the detection of viral mRNAs associated with HHV-6 replication were carried out. In order to test these detection techniques in a context of reactivation, they were applied to blood samples from transplanted patients. The two methods were proved to be effective to highlight the reactivation of HHV-6. Then in the second time, the effect of NF-κB transcription factor on immediate early genes transcription of HHV-6 was investigated. For this purpose, a NF-κB super-repressor (IκBαMut) was transfected in cells permissive to HHV-6 growth. By inhibiting the canonical pathway of NF-κB induction, a reduction in the replication of the virus, demonstrated by a decrease in viral mRNA transcription using a quantitative RT-PCR method and by a reduction in the number of infected cells using an immunofluorescence assay, was observed. Thus an important role for NF-κB transcription factor in the multiplication of virus HHV-6 was shown
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Porée, Benoît. "Effets de l'interleukine-6 (IL-6), de son récepteur soluble (sIL-6R) et du facteur de transcription Erg sur l'expression du collagène de type II dans des chondrocytes articulaires." Caen, 2007. http://www.theses.fr/2007CAEN2060.
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Le collagène de type II est un homotrimère de chaînes α1(II) codées par le gène COL2A1. La synthèse de ce marqueur phénotypique du cartilage est fortement altérée lors de l'arthrose. L'IL-6 est une cytokine proinflammatoire nécessitant la coopération du récepteur soluble sIL-6R pour exercer ses effets. Ce mécanisme pallie l'absence totale ou partielle du récepteur membranaire IL-6R dans certains types cellulaires, dont les chondrocytes. Notre étude démontre que l'IL-6 et/ou sIL-6R inhibent la transcription du gène COL2A1 via une région promotrice comprise entre -63 et -35 pb. Cette inhibition met en jeu les facteurs de transcription Sp1 et Sp3 dont l'activité de liaison au niveau du site -41/-33 pb est réduite sous l'action du duo cytokinique. Par ailleurs, la cytokine et/ou son récepteur soluble diminuent le ratio Sp1/Sp3. L'inhibition fonctionnelle de Sp1 et/ou Sp3, par des leurres oligonucléotidiques ou siRNA, abolit les effets délétères de l'IL-6 et/ou sIL-6R sur la transcription du gène COL2A1, suggérant l'implication d'un complexe hétérotypique Sp1/Sp3 dans le mécanisme réactionnel régi par le complexe IL-6/sIL-6R. De plus, il apparaît que les histones désacétylases puissent intervenir dans ce processus, comme l'atteste les expériences utilisant la trichostatine A, ainsi que les co-immunoprécipitations démontrant une interaction physique entre Sp1 et HDAC1. Dans une seconde partie, nous nous sommes intéressés au facteur de transcription Erg. Ce dernier appartient à la famille des protéines ETS et apparaît indispensable à la mise en place du cartilage articulaire lors de l'embryogenèse. Nous montrons ainsi que des surexpressions de ce facteur dans des chondrocytes articulaires de lapin, augmentent la production du collagène de type II via un contrôle transcriptionnel. Cette stimulation s'exerce au niveau d'une région de l'amplificateur intronique comprise entre +2 127 et +2 384 pb. Au contraire, des surexpressions d'une protéine Erg tronquée, restreinte au domaine de liaison ETS, n'exercent aucun effet sur l'activité transcriptionnelle de COL2A1. En revanche, elle entre en compétition avec la protéine complète et annule ses effets stimulateurs. Le facteur Erg stimule également les expressions de Sp1, Sp3 et Sox9, suggérant que ces facteurs puissent intervenir dans la stimulation exercée par ErgType II collagen is composed of α1(II) chains encoded by the COL2A1 gene. Alteration of this cartilage marker is a common feature of osteoarthritis. IL-6, a pro-inflammatory cytokine, needs to exert its effects in some cases, a soluble form of receptor, sIL-6R, which exerts agonistic action. This mechanism can make up for the partial or total absence of membrane anchored IL-6 receptors in some cell types, such as chondrocytes. Our study shows that IL-6 and/or sIL-6R inhibit COL2A1 gene transcription by a -63/-35 sequence. This inhibition implies Sp1 and Sp3 transcription factors whose DNA-binding activity is decreased to the -41/-33 bp site by both IL-6 and sIL-6R. Knock-down of Sp1/Sp3 by siRNA and decoy strategies were found to prevent the IL-6 and/or sIL-6R induced inhibition of COL2A1 transcription, indicating that a heterotypic Sp1/Sp3 complex is required for down-regulation of the target gene. Additionally, experiments using trichostatin A demonstrate that HDAC activity is involved in this inhibitory process, and Sp1 was shown to interact with HDAC1. In a second part, we investigated the effects of Erg that belongs to the ETS family of transcription factors and that plays a key role in cartilage formation. Indeed, we show that overexpression of Erg in rabbit articular chondrocytes, increase type II collagen production through a transcriptional control. This factor up-regulates COL2A1 gene transcription by a first intron sequence localised between + 2 127 and + 2 384 bp. On the contrary, overexpression of a dominant-negative protein restricted to the ETS domain dn-Erg, shows no effect on the COL2A1 transcriptional activity. On the other hand, dn-Erg enters in competition with the native protein and abrogates its stimulating effects. Erg also stimulates Sp1, Sp3 and Sox9 expressions, suggesting that these factors can be involved in Erg induced stimulation of COL2A1
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Debuisson, Delphine. "Rétrocontrôle des réponses Th2 par l'interleukine-6 et identification d'un nouveau facteur de transcription exprimé par les lymphocytes T helper folliculaires." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209158.
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L’objectif de notre travail a été de caractériser le rôle de l’IL-6 dans la différenciation des lymphocytes Tfh et des lymphocytes Th2. Les lymphocytes Tfh ont pour fonction d’aider les lymphocytes B à produire des anticorps indispensables pour nous protéger contre divers pathogènes. Les lymphocytes Th2, quant à eux, sont spécialisés dans l’élimination de parasites extracellulaires tels que les helminthes.Dans un premier temps, nous avons voulu identifier les gènes dont l’expression est induite par l’IL-6, avec comme objectif une meilleure compréhension des mécanismes permettant aux lymphocytes T de se différencier en cellules Tfh.
Au cours de notre travail, nous avons identifié le facteur de transcription, MyoR (Myogenic Repressor) comme étant exprimé au sein des lymphocytes T helper et dont l’expression est induite par l’IL-6. Nos observations expérimentales ont démontré que le facteur MyoR n’est pas indispensable pour la différenciation des lymphocytes Tfh, ni pour leur fonction. Cependant, l’expression de l’ARNm codant pour MyoR pourrait être utilisée comme un biomarqueur des cellules Tfh in vitro ou in vivo.
Nous avons ensuite caractérisé la réponse immune induite in vivo par des cellules présentatrices d’antigènes issues de souris déficientes pour l’IL-6. Cette approche nous a permis de mettre en évidence le rôle immunosuppresseur de l’IL-6 sur le développement des réponses de type Th2. En effet, nous avons montré que l’injection de BMDCs (Bone Marrow derived dendritic cells) IL-6-/- dans des souris receveuses de type sauvage induisent une réponse Th2 augmentée in vivo.
Nos résultats suggèrent que l’inhibition de la réponse Th2 par l’IL-6 in vivo et in vitro pourrait impliquer la présence d’un ou de plusieurs miRNAs.
Cette inhibition pourrait être un mécanisme de rétrocontrôle afin d’éviter une exacerbation de la réponse immune Th2.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
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Masson, Christel. "Caractérisation de l'expression du gène KIN17 humain lors de la réponse cellulaire aux agents génotoxiques et dans certains tissus tumoraux." Paris 11, 2001. http://www.theses.fr/2001PA11T029.
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Maintenir l'intégrité du matériel génétique de toute cellule vivante face à des altérations d'origine endogène ou exogène, est un problème crucial auquel tout organisme est confronté. Les lésions induites dans l'ADN peuvent interférer avec des processus tels que la réplication et la transcription et entraîner une désorganisation de l'activité cellulaire pouvant conduire à la mort de la cellule. J'ai caractérisé l'expression du gène humain KIN17 après traitement par différents agents génotoxiques. La protéine KIN17 possède une région centrale homologue à un domaine de fixation à l'ADN dans la partie C-terminale de la protéine RecA d'E. Coli. RecA est essentielle à la recombinaison génétique, à la réponse cellulaire aux rayonnements et à la mutagenèse. Mes résultats indiquent une participation active de la protéine KIN17 dans la réponse aux dommages de l'ADN produit par les ultraviolets C (UVC) et les rayonnements gamma (γ). Les cinétiques d'expression du gène KIN17 sont différentes selon la nature de l'agent génotoxique. Compte tenude mes résultats, j'ai cherché à identifier les mécanismes responsables de cette réponse au stress génotoxique en utilisant des lignées cellulaires mutées pour le gène p53 et des cellules exprimant un mutant dominant négatif du facteur de transcription ATF2 : J'ai constaté que l'augmentation de l'expression du gène KIN17 était indépendante de p53 après irradiation γ et UVC. En revanche, ATF2 semble contrôler l’expression du gène KIN17 après γ. L'analyse de l'expression du gène KIN17 dans des cellules déficientes dans la réparation par excision de l'ADN, indique qu'une réparation efficace est indispensable à l'augmentation transitoire de l'expression du gène KIN17 après irradiation aux UVC. Toutes ces observations montrent que le gène KIN17 intervient dans une voie de signalisation qui pourrait aider à contrebalancer les effets délétères des agents génotoxiques. Des résultats préliminaires sur des hépatocarcinomes humains montrent une augmentation de l'expression du gène KIN17 lors de la progression tumoraleAll organisms are confronted by the crucial problem of protecting the integrity of the genetic material in their cells against alterations provoked by endogenous or exogenous agents. DNA damage may interfere with essential processes such as replication and transcription, thus leading to metabolic disruption or to cell death. Ihave characterized the expression profile of KIN17 gene after treatment with different genotoxic agents. KIN17 protein possesses a core region homologous to the DNA-binding domain located in the C-terminal part of the E. Coli RecA protein. RecA plays an essential role in the cellular response to radiation, in recombination and in mutagenesis. My results indicate that the human kin17 protein actively participates in the cellular response to the DNA damage produced by UVC- and γ-irradiation. The kinetics of KIN17 gene expression differs according to the nature of the genotoxic agent. Considering these results, I tried to identify the mechanisms responsible for this response to genotoxic stress by using cells mutated in the p53 gene or cells expressing a dominant negative mutant for ATF2. I noticed that the increase in KIN17 gene expression was independent of p53. The transcription factor ATF2, on the other hand, appeared to be involved in the control of KIN17 gene expression after γ-irradiation. Using cells deficient for nucleotide excision repair (NER), I have demonstrated that an active NER is necessary for the transient increase in KIN17 gene expression after UVC-irradiation. Taken together, these data indicate the Participation of KIN17 gene in a signalling pathway that may help to counterbalance the deleterious effects of genotoxic agents. Prelirninary results on human hepatocarcinoma show increased expression levels of KIN17 gene during tumoral progression
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Hermitte, Stephanie. "Caractérisation de la différenciation de l'endoderme primitif : Coopération entre la voie de signalisation RTK-FGF et le facteur de transcription Gata 6." Thesis, Université Clermont Auvergne (2017-2020), 2017. http://www.theses.fr/2017CLFAS014.
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A E3.5 jours de développement (E3.5), l’embryon murin se compose d’une monocouche de cellules externes correspondant au Trophectoderme (TE) et d’une masse cellulaire interne (MCI), hétérogène, constituée de deux sous-populations de cellules précurseurs : les cellules épiblastiques (Epi) et les cellules d’endoderme primitif (EPr). NANOG, marqueur épiblastique et GATA6, marqueur de l’EPr, sont co-exprimés à E3.5 dans la MCI puis adoptent une expression exclusive au sein de leur lignage respectif. La différenciation du lignage EPr nécessite l’expression de GATA6 et l’activation de la voie Récepteur Tyrosine Kinase (RTK) activée par le FGF (RTK-FGF) pour l’induction de gènes cibles de GATA6 tels que Sox17 et Gata4.Au cours de ma thèse, j’ai, dans un premier temps, étudié la relation GATA6/voie RTK-FGF lors de l’induction de l’expression des gènes de différenciation de l’EPr. J’ai utilisé des cellules souches embryonnaires murines ES sauvages ou mutantes pour Gata6 (ES Gata6-/-), dans lesquelles j’ai surexprimé différentes formes mutantes de Gata6 inactivées sur les différents résidus identifiés comme potentiellement phosphorylables par la voie RTK-FGF. Ainsi, j’ai analysé l’expression protéique des gènes Sox17 et Gata4 ainsi que des expressions ARN de ces cibles et d’autres gènes caractéristiques exprimés dans l’EPr dans les différentes conditions de surexpression des formes de Gata6 en absence ou présence d’inhibiteurs de la voie RTK-FGF. Ainsi, j’ai pu mettre en évidence que la transmission du signal s’effectue au travers de récepteur au FGF et qu’il existe une compensation entre les branches RTK-MEK-ERK et RTK-PI3K ciblant le résidu Sérine 37 de GATA6. Enfin, les résidus S34 et T509 sont nécessaires et les résidus S34, S37 et T509 semblent coopérer, au travers d’un mécanisme pour le moment non détaillé, pour l’induction des gènes cibles exprimés au sein de l’EPr.Dans un second temps, j’ai débuté la caractérisation phénotypique du rôle des facteurs Dickkopf1 (DKK1), un inhibiteur de la voie WNT/β-caténine, et NOGGIN, un inhibiteur de la voie des Bone Morphogenic Protein (BMP) lors de la différentiation de l’EPr en endoderme pariétal (EP) et viscéral (EV). A l’aide de modèles de souris KO pour DKK1 et NOGGIN, croisées en fond C57Bl6 pur, j’ai pu observer que l’expression d’OCT4 était maintenue au sein des embryons homozygotes mutants pour Dkk1 et double homozygotes mutants pour Dkk1 et Noggin. Cependant, le mécanisme potentiel de compensation ou de coopération de ces deux marqueurs n’est pour le moment pas détaillé précisément et mérite l’analyse d’un plus grand nombre d’embryons mutantsAt E3.5 days of development (E3.5), mouse embryo consists of a monolayer of external cells corresponding to Trophectoderme (TE) and of an intern cell mass (ICM), heterogeneous, constituted by two subpopulations of precursory cells: epiblastic cells (Epi) and primitive endoderm cells (EPr). NANOG, an Epi marker and GATA6, a PrE marker, are co-expressed at E3,5 in the MCI and then adopt an exclusive expression within their respective lineage. EPr differentiation requires both expression of GATA6 and RTK pathway, activated by FGF ligand, in order to induce late markers Sox17 and Gata4 expression.First, I studied the relation GATA6/RTK during this process to understand the mechanism of induction of these target genes during final EPr differentiation. I used embryonic stem cells ES WT or Gata6 mutants (ES Gata6-/-), in which I transfected various Gata6 mutant constructions on different residues characterized as potentially phosphorylable by the RTK pathway. So, I analyzed protein expression of Sox17 and Gata4 target genes as well as RNA expression of characteristic genes expressed in the EPr in different inhibition conditions of RTK pathway. So, I was able to highlight that the transmission of the signal is made through the FGF receptor (FGFR1) and that there is compensation between RTK-MEK-ERK and RTK-PI3K pathways highlighted by later Gata6 overexpression of certain mutant forms. Finally, residue S34, S37 and T509 seems to cooperate, through a mechanism not detailed for the moment, for the induction of the EPr target genes.Then, I was interested to phenotypically characterize the role of Dickkopf1 (DKK1), an inhibitor of the WNT/β-catenin pathway, and NOGGIN, an inhibitor of the Bone Morphogenic Protein (BMP) pathway during the EPr differentiation in parietal endoderm (EP) and visceral (EV). Using models of mouse KO for Dkk1 and Noggin, met in pure background C57Bl6, I was able to observe that OCT4 expression was maintained within the Dkk1-/-, and Dkk1-/- Noggin-/- embryos. However, the potential compensation or cooperation mechanism of these two markers is not understanding well for the moment and deserves the analysis of a largest mutant embryos number
Books on the topic "Facteur de transcription ATF-6"
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Ladunga, Istvan, ed. Computational Biology of Transcription Factor Binding. Totowa, NJ: Humana Press, 2010. http://dx.doi.org/10.1007/978-1-60761-854-6.
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Raju, Raghavan, and Irshad H. Chaudry. The host response to hypoxia in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0305.
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The hypoxic response of the host is complex. While the oxygen-sensing intracellular machinery attempts to restore cellular homeostasis by augmenting respiration and blood flow, events such as severe haemorrhage lead to whole body hypoxia and decreased mitochondrial function. Immunological perturbations following severe haemorrhage may result in multiple organ dysfunction and sepsis, while impaired perfusion may lead to microvascular injury and local hypoxia. Trauma-haemorrhage or hypoxic exposure in animals causes a systemic inflammatory response, decreased antigen presentation by peritoneal macrophages, hypoxaemia and initiation of endoplasmic reticulum stress. In response, the protein level of the oxygen-sensing transcription factor, hypoxia inducible factor (HIF)-1 increases; this leads to the regulation of expression of a number of genes resulting in decreased mitochondrial ATP production, but enhanced glycolytic processes, thus shifting the energy balance. In addition, sustained tissue hypoxia leads to increased free radical production and cellular apoptosis. Though the initial host response to hypoxia may be protective, sustained hypoxia becomes detrimental to the tissues and the organism as a whole.
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Alves, Ines Teles, Jan Trapman, and Guido Jenster. Molecular biology of prostate cancer. Edited by James W. F. Catto. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199659579.003.0059.
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Prostate cancer is a heterogeneous disease that arises through the acquisition of key malignant hallmarks. At the molecular level, prostate tumours are dependent upon the androgen receptor pathway, which affects cell function, growth, and behaviour through downstream androgen-regulated genes. Prostate cancer requires this activity and manipulates the AR pathway to maintain signalling. For example, mutation of the AR (to bind ligands other than androgens) or amplification/duplication of the AR allows signalling to continue in the absence of testosterone. Around 50% of prostate cancers have a gene fusion between the androgen-regulated component of the TMPRSS2 gene and a transcription factor (e.g. ETS family members ERG and ETV1). This results in aberrant androgen stimulated cell growth. Current research is using molecular knowledge to identify biomarkers, such as PCA3, and new therapies, such as enzalutamide or abiraterone acetate.
Book chapters on the topic "Facteur de transcription ATF-6"
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Hai, Tsonwin, Johnna Dominick, and Kun Huang. "ATF3 Activating Transcription Factor 3." In Encyclopedia of Signaling Molecules, 467–74. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_612.
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Biswas-Fiss, Esther E., Stephanie Affet, Malissa Ha, Takaya Satoh, Joe B. Blumer, Stephen M. Lanier, Ana Kasirer-Friede, et al. "ATF3 Activating Transcription Factor 3." In Encyclopedia of Signaling Molecules, 169–76. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_612.
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Shouksmith, Andrew E., and Patrick T. Gunning. "Chapter 6. Targeting Signal Transducer and Activator of Transcripion (STAT) 3 with Small Molecules." In Small-molecule Transcription Factor Inhibitors in Oncology, 147–68. Cambridge: Royal Society of Chemistry, 2018. http://dx.doi.org/10.1039/9781782624011-00147.
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Mendonca, Patricia, and Karam F. A. Soliman. "Nutraceutical Activation of the Transcription Factor Nrf2 as a Potential Approach for Modulation of Aging." In Nutraceuticals for Aging and Anti-Aging, 113–31. Boca Raton: CRC Press, 2021. http://dx.doi.org/10.1201/9781003110866-6.
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Hocke, G., G. Baffet, M. Z. Cui, T. Brechner, D. Barry, A. Goel, R. Fletcher, C. Abney, M. Hattori, and H. Fey. "Transcriptional Control of Liver Acute Phase Genes by Interleukin-6 and Leukemia Inhibitory Factor." In Molecular Aspects of Inflammation, 147–66. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-76412-7_12.
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Akira, Shizuo, Hiroshi Isshiki, Toshihiro Nakajima, Shigemi Kinoshita, Yukihiro Nishio, Shunji Natsuka, and Tadamitsu Kishimoto. "Regulation of Expression of the Interleukin 6 Gene: Structure and Function of the Transcription Factor NF-IL6." In Novartis Foundation Symposia, 47–67. Chichester, UK: John Wiley & Sons, Ltd., 2007. http://dx.doi.org/10.1002/9780470514269.ch4.
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Kojima, Hirotada, Hiroyuki Kunimoto, Toshiaki Inoue, and Koichi Nakajima. "Interleukin-6 Induces Premature Senescence Involving Signal Transducer and Activator of Transcription 3 and Insulin-Like Growth Factor-Binding Protein 5." In Tumor Dormancy, Quiescence, and Senescence, Volume 2, 53–60. Dordrecht: Springer Netherlands, 2013. http://dx.doi.org/10.1007/978-94-007-7726-2_6.
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Hai, T., D. Lu, and C. C. Wolford. "TRANSCRIPTION FACTORS | ATF." In Encyclopedia of Respiratory Medicine, 257–60. Elsevier, 2006. http://dx.doi.org/10.1016/b0-12-370879-6/00388-4.
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Jackson, Stephen p. "Identification and characterization of eukaryotic transcription factors." In Gene Transcription, 189–242. Oxford University PressOxford, 1993. http://dx.doi.org/10.1093/oso/9780199632923.003.0006.
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Abstract An important and widely used mechanism for regulating gene expression in eukaryotic organisms is that of modulating the efficiency of transcriptional initiation. Molecular genetic analysis of transcriptional promoters recognized by RNA polymerase II has revealed that accurate and efficient transcription requires a variety of cisacting sequence elements. These elements are recognized and bound by sequencespecific DNAbinding transcription factor proteins that then serve to either activate, or in some cases repress, transcriptional initiation by the general transcriptional apparatus (1-4). A great many sequencespecific transcription factors exist; they differ from one another in the DNA sequence(s) that they recognize and in the way that they are regulated themselves. For example, some transcription factor are restricted to particular cell types, others are expressed only at certain stages of development, while yet others are activated only in response to a particular physilogoical agent such as a hormone. By employing different combinations of these sequencespecific factors, highly complex and unique patterns of gene expression are achieved. This chapter describes various approaches that are used to define, purify, and characterize sequencespecific transcription factor proteins.
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"ATF2 (activating transcription factor)." In Encyclopedia of Genetics, Genomics, Proteomics and Informatics, 156. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_1292.
Full textConference papers on the topic "Facteur de transcription ATF-6"
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Chen, B., J. Wang, L. Shang, and J. Solway. "Krüppel-Like Factor 6 Gene Expression Is Regulated by GATA5 Transcription Factor." In American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX. American Thoracic Society, 2019. http://dx.doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a3964.
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Liu, Ka, Richard L. Smith, Trang Nguyen-Vu, Nicholes R. Candelaria, Colin M. Rogerson, W. Evan Johnson, Edwin Cheung, et al. "Abstract 3107: Runt-related transcription factor 1 (RUNX1) is involved in transcriptional repression by estrogen receptor and breast cancer cell proliferation." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-3107.
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Wu, Q. Y., B. R. Bahnak, L. Coulombel, J. P. Caen, G. Pietu, and D. Meyer. "VON WILLEBRAND FACTOR mRNA IS SEVERELY REDUCED IN PIGS WITH HOMOZYGOUS VON WILLEBRAND DISEASE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644113.
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Porcine von Willebrand disease (vWD), an autosomal recessive disorder, is similar to some of the severe forms of vWD in humans and is characterized by a prolonged bleeding time and very low or undetectable amounts of von Willebrand factor (vWF) antigen and activity in plasma, platelets and endothelial cells. The molecular events that control the lack of expression of vWF in the vWD pigs is not known and could be at the transcriptional or post-transcriptional level. Lungs from normal and two homozygous vWD pigs were extracted immediately after harvesting of the animals and placed on dry ice. Tissues were homogenized in 6 M guanidinium thiocyanate and RNA isolated by centrifugation through cesium chloride. Total RNA was analyzed by Northern hybridization including dénaturation in glyoxal, electrophoresis in 1.0 % agarose-2.2 M formaldehyde gels and transfer onto nitrocellulose. Messenger RNA was detected with a nick-translated human vWF cDNA probe or a human actin control probe. The vWF probe, cloned from a human lung library, was 2,280 bp in length and spanned nucleotides 960 to 3,240 of the human cDNA. These human probes were considered valid to detect levels of porcine vWF and actin mRNA because they hybridized with restriction enzyme digested genomic DNA from normal and vWD pig leucocytes under conditions of high stringency. The size of the vWF mRNA in the normal pigs after Northern hybridization was approximately 9.0 kb, similar to that of human vWF mRNA, and was easily detectable at the lowest concentration of RNA blotted (5 ug). In contrast, vWF mRNA from vWD pigs was at the lower limit of detection even at 10 ug of total RNA blotted. Nevertheless, although at extremely low levels, vWF mRNA from vWD pigs appeared to be the same size as the normal mRNA. These results agree with observations on the relationship of vWF secreted from 24 hr. cultures of endothelial cells from the pulmonary artery of normal and vWD pigs where the vWF levels were 0.90 and 0.06 U/108 cells, respectively. Therefore, it appears that the very low expression of vWF in the vWD pigs is due to a lack of transcription of the vWF gene. At this time, however, turnover of unstable transcripts in the vWD pigs can not be ruled out.
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Lee, Seong-Ho, Jae Hoon Bahn, Nichelle Whitlock, and Seung J. Baek. "Abstract 2035: Activating transcription factor 2 (ATF2) controls tolfenamic acid-induced ATF3 expression via MAP kinase pathways." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-2035.
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Stegmaier, Kimberly, Brian Crompton, Jonathan Jessneck, Kenneth Ross, Supriya Gupta, Lynn Ver Plank, Wendy Winckler, and Nicola Tolliday. "Abstract LB-240: Modulating transcription factor abnormalities in pediatric cancer." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-lb-240.
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de Beyer, D., F. Kraus, D. Mayr, A. Chelariu-Raicu, J. Reichenbach, N. E. Topalov, C. Tauber, et al. "Prognostische Relevanz des activating transcription factor 4 (ATF4) im Ovarialkarzinom." In 65. Kongress der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe e. V. Georg Thieme Verlag KG, 2024. http://dx.doi.org/10.1055/s-0044-1790669.
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Dixit, VM. "Abstract BS1-1: Transcription factor stability and stem cell maintenance." In Abstracts: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, Texas. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.sabcs16-bs1-1.
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St. Clair, Caryn M., Stephanie L. Wethington, Maria Bisogna, Fanny Dao, Petar Jelinic, and Douglas A. Levine. "Abstract 3158: Transcription factor SOX11 decreases viability in ovarian carcinoma cells." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-3158.
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Lee, Kyung Hee, Sung Ae Koh, Ha Young Lee, Min Kyoung Kim, Kyeong Ok Kim, Se Young Lee, Byung Ik Jang, et al. "Abstract 998: Downregulation of survivin suppresses uPA through transcription factor JunB." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-998.
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Yu, Mei, David Zloty, Robert H. Bell, Anne Haegert, Nicholas Carr, Jerry Shapiro, Bryce Cowan, Larry Warshawski, and Kevin J. McElwee. "Abstract 241: Transcription factor RBP-J-mediated signaling regulates basal cell carcinoma growth." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-241.
Full textReports on the topic "Facteur de transcription ATF-6"
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Pichersky, Eran, Alexander Vainstein, and Natalia Dudareva. Scent biosynthesis in petunia flowers under normal and adverse environmental conditions. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7699859.bard.
Full textAbstract:
The ability of flowering plants to prosper throughout evolution, and for many crop plants to set fruit, is strongly dependent on their ability to attract pollinators. To that end many plants synthesize a spectrum of volatile compounds in their flowers. Scent is a highly dynamic trait that is strongly influenced by the environment. However, with high temperature conditions becoming more common, the molecular interplay between this type of stress and scent biosynthesis need to be investigated. Using petunia as a model system, our project had three objectives: (1) Determine the expression patterns of genes encoding biosynthetic scent genes (BSGs) and of several genes previously identified as encoding transcription factors involved in scent regulation under normal and elevated temperature conditions. (2) Examine the function of petunia transcription factors and a heterologous transcription factor, PAPl, in regulating genes of the phenylpropanoid/benzenoid scent pathway. (3) Study the mechanism of transcriptional regulation by several petunia transcription factors and PAPl of scent genes under normal and elevated temperature conditions by examining the interactions between these transcription factors and the promoters of target genes. Our work accomplished the first two goals but was unable to complete the third goal because of lack of time and resources. Our general finding was that when plants grew at higher temperatures (28C day/22C night, vs. 22C/16C), their scent emission decreased in general, with the exception of a few volatiles such as vanillin. To understand why, we looked at gene transcription levels, and saw that generally there was a good correlation between levels of transcriptions of gene specifying enzymes for specific scent compounds and levels of emission of the corresponding scent compounds. Enzyme activity levels, however, showed little difference between plants growing at different temperature regimes. Plants expressing the heterologous gene PAPl showed general increase in scent emission in control temperature conditions but emission decreased at the higher temperature conditions, as seen for control plants. Finally, expression of several transcription factor genes decreased at high temperature, but expression of new transcription factor, EOB-V, increased, implicating it in the decrease of transcription of BSGs. The major conclusion of this work is that high temperature conditions negatively affect scent emission from plants, but that some genetic engineering approaches could ameliorate this problem.
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Arazi, Tzahi, Vivian Irish, and Asaph Aharoni. Micro RNA Targeted Transcription Factors for Fruit Quality Improvement. United States Department of Agriculture, July 2008. http://dx.doi.org/10.32747/2008.7592651.bard.
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Fruits are unique to flowering plants and represent an important component of human and animal diets. Development and maturation of tomato fruit is a well-programmed process, and yet, only a limited number of factors involved in its regulation have been characterized. Micro-RNAs (miRNAs) are small, endogenous RNAs that regulate gene expression in animals and plants. Plant miRNAs have a vital role in the generation of plant forms through post-transcriptional regulation of the accumulation of developmental regulators, especially transcription factors. Recently, we and others have demonstrated that miRNAs and other type of small RNAs are expressed in tomato fruit, and target putative transcription factors during its development and maturation. The original objectives of the approved proposal were: 1. To identify fruit miRNA transcription factor target genes through a bioinformatic approach. 2. To identify fruit miRNA transcription factor target genes up-regulated in tomato Dicer-like 1 silenced fruit. 3. To establish the biological functions of selected transcription factors and examine their utility for improving fleshy fruit quality trait. This project was approved by BARD as a feasibility study to allow initial experiments to peruse objective 2 as described above in order to provide initial evidence that miRNAs do play a role in fruit development. The approach planned to achieve objective 2, namely to identify miRNA transcription factor targets was to clone and silence the expression of a tomato DCL1 homolog in different stages of fruit development and examine alterations to gene expression in such a fruit in order to identify pathways and target genes that are regulated by miRNA via DCL1. In parallel, we characterized two transcription factors that are regulated by miRNAs in the fruit. We report here on the cloning of tomato DCL1 homolog, characterization of its expression in fruit flesh and peel of wild type and ripening mutants and generation of transgenic plants that silence SlDCL1 specifically in the fruit. Our results suggest that the tomato homolog of DCL1, which is the major plant enzyme involved in miRNA biogenesis, is present in fruit flesh and peel and differentially expressed during various stages of fruit development. In addition, its expression is altered in ripening mutants. We also report on the cloning and expression analysis of Sl_SBP and Sl_ARF transcription factors, which serve as targets of miR157 and miR160, respectively. Our data suggest that Sl_SBP levels are highest during fruit ripening supporting a role for this gene in that process. On the other hand Sl_ARF is strongly expressed in green fruit up to breaker indicating a role for that gene at preripening stage which is consistent with preliminary in_situ analyses that suggest expression in ovules of immature green fruit. The results of this feasibility study together with our previous results that miRNAs are expressed in the fruit indeed provide initial evidence that these regulators and their targets play roles in fruit development and ripening. These genes are expected to provide novel means for genetic improvement of tomato fleshy fruit.
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Fromm, Hillel, Paul Michael Hasegawa, and Aaron Fait. Calcium-regulated Transcription Factors Mediating Carbon Metabolism in Response to Drought. United States Department of Agriculture, June 2013. http://dx.doi.org/10.32747/2013.7699847.bard.
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Original objectives: The long-term goal of the proposed research is to elucidate the transcription factors, genes and metabolic networks involved in carbon metabolism and partitioning in response to water deficit. The proposed research focuses on the GTLcalcium/calmodulinbindingTFs and the gene and metabolic networks modulated by these TFs in Arabidopsis thaliana. The specific objectives are as follows. Objective-1 (USA): Physiological analyses of GTL1 loss- and gain-of-function plants under water sufficient and drought stress conditions Objective 2 (USA / Israel-TAU): Characterizion of GTL target genes and bioinformatic analysis of data to eulcidate gene-network topology. Objective-3 (Israel-TAU): Regulation of GTLmediated transcription by Ca²⁺/calmodulin: mechanism and biological significance. Objective-4 (Israel-BGU): Metabolic networks and carbon partitioning in response to drought. Additional direction: In the course of the project we added another direction, which was reported in the 2nd annual report, to elucidate genes controlling drought avoidance. The TAU team has isolated a few unhydrotropic (hyd) mutants and are in the process of mapping these mutations (of hyd13 and hyd15; see last year's report for a description of these mutants under salt stress) in the Arabidopsis genome by map-based cloning and deep sequencing. For this purpose, each hyd mutant was crossed with a wild type plant of the Landsberg ecotype, and at the F2 stage, 500-700 seedlings showing the unhydrotropic phenotype were collected separately and pooled DNA samples were subkected to the Illumina deep sequencing technology. Bioinformatics were used to identify the exact genomic positions of the mutations (based on a comparison of the genomic sequences of the two Arabidopsis thaliana ecotypes (Columbia and Landsberg). Background: To feed the 9 billion people or more, expected to live on Earth by the mid 21st century, the production of high-quality food must increase substantially. Based on a 2009 Declaration of the World Summit on Food Security, a target of 70% more global food production by the year 2050 was marked, an unprecedented food-production growth rate. Importantly, due to the larger areas of low-yielding land globally, low-yielding environments offer the greatest opportunity for substantial increases in global food production. Nowadays, 70% of the global available water is used by agriculture, and 40% of the world food is produced from irrigated soils. Therefore, much needs to be done towards improving the efficiency of water use by plants, accompanied by increased crop yield production under water-limiting conditions. Major conclusions, solutions and achievements: We established that AtGTL1 (Arabidopsis thaliana GT-2 LIKE1) is a focal determinant in water deficit (drought) signaling and tolerance, and water use efficiency (WUE). The GTL1 transcription factor is an upstream regulator of stomatal development as a transrepressor of AtSDD1, which encodes a subtilisin protease that activates a MAP kinase pathway that negatively regulates stomatal lineage and density. GTL1 binds to the core GT3 cis-element in the SDD1 promoter and transrepresses its expression under water-sufficient conditions. GTL1 loss-of-function mutants have reduced stomatal number and transpiration, and enhanced drought tolerance and WUE. In this case, higher WUE under water sufficient conditions occurs without reduction in absolute biomass accumulation or carbon assimilation, indicating that gtl1-mediated effects on stomatal conductance and transpiration do not substantially affect CO₂ uptake. These results are proof-of-concept that fine-tuned regulation of stomatal density can result in drought tolerance and higher WUE with maintenance of yield stability. Implications: Accomplishments during the IS-4243-09R project provide unique tools for continued discovery research to enhance plant drought tolerance and WUE.
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Barg, Rivka, Erich Grotewold, and Yechiam Salts. Regulation of Tomato Fruit Development by Interacting MYB Proteins. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7592647.bard.
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Background to the topic: Early tomato fruit development is executed via extensive cell divisions followed by cell expansion concomitantly with endoreduplication. The signals involved in activating the different modes of growth during fruit development are still inadequately understood. Addressing this developmental process, we identified SlFSM1 as a gene expressed specifically during the cell-division dependent stages of fruit development. SlFSM1 is the founder of a class of small plant specific proteins containing a divergent SANT/MYB domain (Barg et al 2005). Before initiating this project, we found that low ectopic over-expression (OEX) of SlFSM1 leads to a significant decrease in the final size of the cells in mature leaves and fruits, and the outer pericarp is substantially narrower, suggesting a role in determining cell size and shape. We also found the interacting partners of the Arabidopsis homologs of FSM1 (two, belonging to the same family), and cloned their tomato single homolog, which we named SlFSB1 (Fruit SANT/MYB–Binding1). SlFSB1 is a novel plant specific single MYB-like protein, which function was unknown. The present project aimed at elucidating the function and mode of action of these two single MYB proteins in regulating tomato fruit development. The specific objectives were: 1. Functional analysis of SlFSM1 and its interacting protein SlFSB1 in relation to fruit development. 2. Identification of the SlFSM1 and/or SlFSB1 cellular targets. The plan of work included: 1) Detailed phenotypic, histological and cellular analyses of plants ectopically expressing FSM1, and plants either ectopically over-expressing or silenced for FSB1. 2) Extensive SELEX analysis, which did not reveal any specific DNA target of SlFSM1 binding, hence the originally offered ChIP analysis was omitted. 3) Genome-wide transcriptional impact of gain- and loss- of SlFSM1 and SlFSB1 function by Affymetrix microarray analyses. This part is still in progress and therefore results are not reported, 4) Search for additional candidate partners of SlFSB1 revealed SlMYBI to be an alternative partner of FSB1, and 5) Study of the physical basis of the interaction between SlFSM1 and SlFSB1 and between FSB1 and MYBI. Major conclusions, solutions, achievements: We established that FSM1 negatively affects cell expansion, particularly of those cells with the highest potential to expand, such as the ones residing inner to the vascular bundles in the fruit pericarp. On the other hand, FSB1 which is expressed throughout fruit development acts as a positive regulator of cell expansion. It was also established that besides interacting with FSM1, FSB1 interacts also with the transcription factor MYBI, and that the formation of the FSB1-MYBI complex is competed by FSM1, which recognizes in FSB1 the same region as MYBI does. Based on these findings a model was developed explaining the role of this novel network of the three different MYB containing proteins FSM1/FSB1/MYBI in the control of tomato cell expansion, particularly during fruit development. In short, during early stages of fruit development (Phase II), the formation of the FSM1-FSB1 complex serves to restrict the expansion of the cells with the greatest expansion potential, those non-dividing cells residing in the inner mesocarp layers of the pericarp. Alternatively, during growth phase III, after transcription of FSM1 sharply declines, FSB1, possibly through complexing with the transcription factor MYBI serves as a positive regulator of the differential cell expansion which drives fruit enlargement during this phase. Additionally, a novel mechanism was revealed by which competing MYB-MYB interactions could participate in the control of gene expression. Implications, both scientific and agricultural: The demonstrated role of the FSM1/FSB1/MYBI complex in controlling differential cell growth in the developing tomato fruit highlights potential exploitations of these genes for improving fruit quality characteristics. Modulation of expression of these genes or their paralogs in other organs could serve to modify leaf and canopy architecture in various crops.
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Funkenstein, Bruria, and Shaojun (Jim) Du. Interactions Between the GH-IGF axis and Myostatin in Regulating Muscle Growth in Sparus aurata. United States Department of Agriculture, March 2009. http://dx.doi.org/10.32747/2009.7696530.bard.
Full textAbstract:
Growth rate of cultured fish from hatching to commercial size is a major factor in the success of aquaculture. The normal stimulus for muscle growth in growing fish is not well understood and understanding the regulation of muscle growth in fish is of particular importance for aquaculture. Fish meat constitutes mostly of skeletal muscles and provides high value proteins in most people's diet. Unlike mammals, fish continue to grow throughout their lives, although the size fish attain, as adults, is species specific. Evidence indicates that muscle growth is regulated positively and negatively by a variety of growth and transcription factors that control both muscle cell proliferation and differentiation. In particular, growth hormone (GH), fibroblast growth factors (FGFs), insulin-like growth factors (IGFs) and transforming growth factor-13 (TGF-13) play critical roles in myogenesis during animal growth. An important advance in our understanding of muscle growth was provided by the recent discovery of the crucial functions of myostatin (MSTN) in controlling muscle growth. MSTN is a member of the TGF-13 superfamily and functions as a negative regulator of skeletal muscle growth in mammals. Studies in mammals also provided evidence for possible interactions between GH, IGFs, MSTN and the musclespecific transcription factor My oD with regards to muscle development and growth. The goal of our project was to try to clarify the role of MSTNs in Sparus aurata muscle growth and in particular determine the possible interaction between the GH-IGFaxis and MSTN in regulating muscle growth in fish. The steps to achieve this goal included: i) Determining possible relationship between changes in the expression of growth-related genes, MSTN and MyoD in muscle from slow and fast growing sea bream progeny of full-sib families and that of growth rate; ii) Testing the possible effect of over-expressing GH, IGF-I and IGF-Il on the expression of MSTN and MyoD in skeletal muscle both in vivo and in vitro; iii) Studying the regulation of the two S. aurata MSTN promoters and investigating the possible role of MyoD in this regulation. The major findings of our research can be summarized as follows: 1) Two MSTN promoters (saMSTN-1 and saMSTN-2) were isolated and characterized from S. aurata and were found to direct reporter gene activity in A204 cells. Studies were initiated to decipher the regulation of fish MSTN expression in vitro using the cloned promoters; 2) The gene coding for saMSTN-2 was cloned. Both the promoter and the first intron were found to be polymorphic. The first intron zygosity appears to be associated with growth rate; 3) Full length cDNA coding for S. aurata growth differentiation factor-l I (GDF-II), a closely related growth factor to MSTN, was cloned from S. aurata brain, and the mature peptide (C-terminal) was found to be highly conserved throughout evolution. GDF-II transcript was detected by RT -PCR analysis throughout development in S. aurata embryos and larvae, suggesting that this mRNA is the product of the embryonic genome. Transcripts for GDF-Il were detected by RT-PCR in brain, eye and spleen with highest level found in brain; 4) A novel member of the TGF-Bsuperfamily was partially cloned from S. aurata. It is highly homologous to an unidentified protein (TGF-B-like) from Tetraodon nigroviridisand is expressed in various tissues, including muscle; 5) Recombinant S. aurata GH was produced in bacteria, refolded and purified and was used in in vitro and in vivo experiments. Generally, the results of gene expression in response to GH administration in vivo depended on the nutritional state (starvation or feeding) and the time at which the fish were sacrificed after GH administration. In vitro, recombinantsaGH activated signal transduction in two fish cell lines: RTHI49 and SAFI; 6) A fibroblastic-like cell line from S. aurata (SAF-I) was characterized for its gene expression and was found to be a suitable experimental system for studies on GH-IGF and MSTN interactions; 7) The gene of the muscle-specific transcription factor Myogenin was cloned from S. aurata, its expression and promoter activity were characterized; 8) Three genes important to myofibrillogenesis were cloned from zebrafish: SmyDl, Hsp90al and skNAC. Our data suggests the existence of an interaction between the GH-IGFaxis and MSTN. This project yielded a great number of experimental tools, both DNA constructs and in vitro systems that will enable further studies on the regulation of MSTN expression and on the interactions between members of the GHIGFaxis and MSTN in regulating muscle growth in S. aurata.
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Eshed-Williams, Leor, and Daniel Zilberman. Genetic and cellular networks regulating cell fate at the shoot apical meristem. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7699862.bard.
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The shoot apical meristem establishes plant architecture by continuously producing new lateral organs such as leaves, axillary meristems and flowers throughout the plant life cycle. This unique capacity is achieved by a group of self-renewing pluripotent stem cells that give rise to founder cells, which can differentiate into multiple cell and tissue types in response to environmental and developmental cues. Cell fate specification at the shoot apical meristem is programmed primarily by transcription factors acting in a complex gene regulatory network. In this project we proposed to provide significant understanding of meristem maintenance and cell fate specification by studying four transcription factors acting at the meristem. Our original aim was to identify the direct target genes of WUS, STM, KNAT6 and CNA transcription factor in a genome wide scale and the manner by which they regulate their targets. Our goal was to integrate this data into a regulatory model of cell fate specification in the SAM and to identify key genes within the model for further study. We have generated transgenic plants carrying the four TF with two different tags and preformed chromatin Immunoprecipitation (ChIP) assay to identify the TF direct target genes. Due to unforeseen obstacles we have been delayed in achieving this aim but hope to accomplish it soon. Using the GR inducible system, genetic approach and transcriptome analysis [mRNA-seq] we provided a new look at meristem activity and its regulation of morphogenesis and phyllotaxy and propose a coherent framework for the role of many factors acting in meristem development and maintenance. We provided evidence for 3 different mechanisms for the regulation of WUS expression, DNA methylation, a second receptor pathway - the ERECTA receptor and the CNA TF that negatively regulates WUS expression in its own domain, the Organizing Center. We found that once the WUS expression level surpasses a certain threshold it alters cell identity at the periphery of the inflorescence meristem from floral meristem to carpel fate [FM]. When WUS expression highly elevated in the FM, the meristem turn into indeterminate. We showed that WUS activate cytokinine, inhibit auxin response and represses the genes required for root identity fate and that gradual increase in WUCHEL activity leads to gradual meristem enlargement that affect phyllotaxis. We also propose a model in which the direction of WUS domain expansion laterally or upward affects meristem structure differently. We preformed mRNA-seq on meristems with different size and structure followed by k-means clustering and identified groups of genes that are expressed in specific domains at the meristem. We will integrate this data with the ChIP-seq of the 4 TF to add another layer to the genetic network regulating meristem activity.
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Chen, Junping, Zach Adam, and Arie Admon. The Role of FtsH11 Protease in Chloroplast Biogenesis and Maintenance at Elevated Temperatures in Model and Crop Plants. United States Department of Agriculture, May 2013. http://dx.doi.org/10.32747/2013.7699845.bard.
Full textAbstract:
specific objectives of this proposal were to: 1) determine the location, topology, and oligomerization of FtsH11 protease; 2) identify the substrate/s of FtsH11 and the downstream components involved in maintaining thermostability of chloroplasts; 3) identify new elements involved in FtsH11 protease regulatory network related to HT adaptation processes in chloroplast; 4) Study the role of FtsH11 homologs from crop species in HT tolerance. Background to the topic: HT-tolerant varieties that maintain high photosynthetic efficiency at HT, and cope better with daily and seasonal temperature fluctuations are in great need to alleviate the effect of global warming on food production. Photosynthesis is a very complex process requiring accurate coordination of many complex systems and constant adjustments to the changing environments. Proteolytic activities mediated by various proteases in chloroplast are essential part of this process and critical for maintaining normal chloroplast functions under HT. However, little is known about mechanisms that contribute to adaptation of photosynthetic processes to HT. Our study has shown that a chloroplast-targeted Arabidopsis FtsH11 protease plays an essential and specific role in maintaining thermostability of thylakoids and normal photosynthesis at moderate HT. We hypothesized that FtsH11 homologs recently identified in other plant species might have roles similarly to that of AtFtsH1. Thus, dissecting the underlying mechanisms of FtsH11 in the adaptation mechanisms in chloroplasts to HT stress and other elements involved will aid our effort to produce more agricultural products in less favorable environments. Major conclusions, solutions, achievements - Identified the chloroplast inner envelope membrane localization of FtsH11. - Revealed a specific association of FtsH11 with the a and b subunits of CPN60. - Identified the involvement of ARC6, a protein coordinates chloroplast division machineries in plants, in FtsH11 mediated HT adaptation process in chloroplast. -Reveal possible association of a polyribonucleotide nucleotidyltransferase (cpPNPase), coded by At3G03710, with FtsH11 mediated HT adaptation process in chloroplast. - Mapped 4 additional loci in FtsH11 mediated HT adaptation network in chloroplast. - Demonstrated importance of the proteolytic activity of FtsH11 for thermotolerance, in addition to the ATPase activity. - Demonstrated a conserved role of plant FtsH11 proteases in chloroplast biogenesis and in maintaining structural and functional thermostability of chloroplast at elevated temperatures. Implications, both scientific and agricultural:Three different components interacting with FtsH11 were identified during the course of this study. At present, it is not known whether these proteins are directly involved in FtsH11mediated thermotolerance network in chloroplast and/or how these elements are interrelated. Studies aiming to connect the dot among biological functions of these networks are underway in both labs. Nevertheless, in bacteria where it was first studied, FtsH functions in heat shock response by regulating transcription level of σ32, a heat chock factor regulates HSPsexpression. FtsH also involves in control of biosynthesis of membrane components and quality control of membrane proteins etc. In plants, both Arc 6 and CPN60 identified in this study are essential in chloroplast division and developments as mutation of either one impairs chloroplast division in Arabidopsis. The facts that we have found the specific association of both α and β CPN60 with FtsH11 protein biochemically, the suppression/ enhancement of ftsh11 thermosensitive phenotype by arc6 /pnp allele genetically, implicate inter-connection of these networks via FtsH11 mediated network(s) in regulating the dynamic adaptation processes of chloroplast to temperature increases at transcriptional, translational and post-translational levels. The conserved role of FtsH11 proteases in maintaining thermostability of chloroplast at HT demonstrated here provides a foundation for improving crop photosynthetic performance at high temperatures.
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Prusky, Dov, and Jeffrey Rollins. Modulation of pathogenicity of postharvest pathogens by environmental pH. United States Department of Agriculture, December 2006. http://dx.doi.org/10.32747/2006.7587237.bard.
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Until recently, environmental pH was not considered a factor in determining pathogen compatibility. Our hypothesis was that the environmental pH at the infection site, which is dynamically controlled by activities of both the host and the pathogen, regulates the expression of genes necessary for disease development in Colletotrichum gloeosporioides and Sclerotinia sclerotiorum. This form of regulation ensures that genes are expressed at optimal conditions for their encoded activities.Pectate lyase encoded by pelB, has been demonstrated to play a key role in virulence of C. gloeosporioides in avocado fruit. Polyglacturonase synergism with oxalic acid production is considered to be an essential pathogenicity determinant in the interactions of S. sclerotiorum with its numerous hosts. A common regulatory feature of these virulence and pathogenicity factors is their dependence upon environmental pH conditions within the host niche to create optimal conditions for expression and secretion. In this proposal we have examined, 1) the mechanisms employed by these fungi to establish a suitable pH environment, 2) the molecular levels at which genes and gene products are regulated in response to environmental pH, and 3) the molecular basis and functional importance of pH-responsive gene regulation during pathogenicity. The specific objectives of the proposal were: 1. Characterize the mechanism of local pH modulation and the effect of ambient pH on the expression and secretion of virulence factors. 2. Provide evidence that a conserved molecular pathway for pH-responsive gene expression exists in C. gloeosporioides by cloning a pacC gene homologue. 3. Determine the role of pacC in pathogenicity by gene disruption and activating mutations. Major conclusions 1. We determined the importance of nitrogen source and external pH in the secretion of the virulence factor pectate lyase with respect to the ambient pH transcriptional regulator pacC. It was concluded that nitrogen source availability and ambient pH are two independent signals for the transcriptional regulation of genes required for the disease process of C. gloeosporioides and possibly of other pathogens. 2. We also determined that availability of ammonia regulate independently the alkalinization process and pelB expression, pecate lyase secretion and virulence of C. gloeosporioides. 3. Gene disruption of pacC reduced virulence of C. gloeosporioides however did not reduced fully pelB expression. It was concluded that pelB expression is regulated by several factors including pH, nitrogen and carbon sources. 4. Gene disruption of pacC reduced virulence of S. slcerotiourum Creation of a dominant activating
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Levy, Avraham A., and Virginia Walbot. Regulation of Transposable Element Activities during Plant Development. United States Department of Agriculture, August 1992. http://dx.doi.org/10.32747/1992.7568091.bard.
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We have studied the regulation of the maize Ac and MuDR transposable elements activities during plant development. Ac was studied in an heterologous system (transgenic tobacco plants and cell suspensions) while MuDR was studied in the native maize background. The focus of this study was on the transcriptional regulation of Ac and MuDR. For Ac, the major achievements were to show that 1-It is autoregulated in a way that the Ac-encoded transposase can repress the activity of its own promoter; 2-It is expressed at low basal level in all the plant organs that were studied, and its activity is stronger in dividing tissues -- a behaviour reminiscent of housekeeping genes; 3- the activity of Ac promoter is cell cycle regulated -- induced at early S-phase and increasing until mitosis; 4- host factor binding sites were identified at both extremities of Ac and may be important for transposition. For MuDR, It was shown that it encodes two genes, mudrA and mudrB, convergently transcribed from near-identical promoters in the terminal inverted repeats. Distinct 5' start sites, alternative splicing, production of antisense RNA and tissue specificity were all shown to be involved in the regulation of MuDR.
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Coplin, David, Isaac Barash, and Shulamit Manulis. Role of Proteins Secreted by the Hrp-Pathways of Erwinia stewartii and E. herbicola pv. gypsophilae in Eliciting Water-Soaking Symptoms and Initiating Galls. United States Department of Agriculture, June 2001. http://dx.doi.org/10.32747/2001.7580675.bard.
Full textAbstract:
Many bacterial pathogens of plants can inject pathogenicity proteins into host cells using a specialized type III secretion system encoded by hrpgenes. This system deliver effector proteins, into plant cells that function in both susceptible and resistant interactions. We have found that the virulence of Erwinia stewartii(Es; syn. Pantoea stewartii) and Erwinia herbicola pv. gypsophilae (Ehg, syn. Pantoea agglomerans), which cause Stewart's wilt of corn and galls on Gypsophila, respectively, depends on hrpgenes. The major objectives of this project were: To increase expression of hrpgenes in order to identify secreted proteins; to identify genes for proteins secreted by the type-III systems and determine if they are required for pathogenicity; and to determine if the secreted proteins can function within eukaryotic cells. We found that transcription of the hrp and effector genes in Es and Ehg is controlled by at least four genes that constitute a regulatory cascade. Environmental and/or physiological signaling appears to be mediated by the HrpX/HrpY two component system, with HrpX functioning as a sensor-kinase and HrpY as a response regulator. HrpYupregulateshrpS, which encodes a transcriptional enhancer. HrpS then activates hrpL, which encodes an alternate sigma factor that recognizes "hrp boxes". All of the regulatory genes are essential for pathogenicity, except HrpX, which appears only to be required for induction of the HR in tobacco by Es. In elucidating this regulatory pathway in both species, we made a number of significant new discoveries. HrpX is unusual for a sensor-kinase because it is cytoplasmic and contains PAS domains, which may sense the redox state of the bacterium. In Es, a novel methyl-accepting protein may function upstream of hrpY and repress hrp gene expression in planta. The esaIR quorum sensing system in Es represses hrp gene expression in Es in response to cell-density. We have discovered six new type III effector proteins in these species, one of which (DspE in Ehg and WtsE in Es) is common to both pathogens. In addition, Es wtsG, which is a homolog of an avrPpiB from P. syringae pv. pisi, and an Ehg ORF, which is a homolog of P. syringae pv. phaseolicola AvrPphD, were both demonstrated to encode virulence proteins. Two plasmidborne, Ehg Hop proteins, HsvG and PthG, are required for infection of gypsophilia, but interestingly, PthG also acts as an Avr elicitor in beets. Using a calmodulin-dependent adenylate cyclase (cyaA) reporter gene, we were successful in demonstrating that an HsvG-CyaA fusion protein can be transferred into human HeLa cells by the type-III system of enteropathogenic E. coli. This is a highly significant accomplishment because it is the first direct demonstration that an effector protein from a plant pathogenic bacterium is capable of being translocated into a eukaryotic cell by a type-III secretion system. Ehg is considered a limiting factor in Gypsophila production in Israel and Stewart’s Wilt is a serious disease in the Eastern and North Central USA, especially on sweet corn in epidemic years. We believe that our basic research on the characterization of type III virulence effectors should enable future identification of their receptors in plant cells. This may lead to novel approaches for genetically engineering resistant plants by modifying their receptors or inactivating effectors and thus blocking the induction of the susceptible response. Alternatively, hrp gene regulation might also provide a target for plant produced compounds that interfere with recognition of the host by the pathogen. Such strategies would be broadly applicable to a wide range of serious bacterial diseases on many crops throughout the USA and Israel.