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.
Full textBAHR, 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.
Full textTardif, 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.
Full textKeywords. GATA-6, muscle regeneration, mdx, satellite cells
Journiac, Nathalie. "Etude du rôle du facteur de transcription RORα dans la réaction gliale." Paris 6, 2007. http://www.theses.fr/2007PA066031.
Full textGAIRE, 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.
Full textPradeau, Karine. "Réactivation de l'herpèsvirus humain de type 6 (HHV-6) : outils de détection et mécanismes moléculaires." Limoges, 2005. http://www.theses.fr/2005LIMO0027.
Full textHuman 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
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.
Full textType 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
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.
Full textDans 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
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.
Full textAll 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
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.
Full textAt 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
Isnard, Amandine. "Les gènes IL13, STAT6 et IL5 sont impliqués dans la susceptibilité génétique humaine à l'infection par Schistosoma haematobium." Aix-Marseille 2, 2009. http://www.theses.fr/2009AIX20729.
Full textGiroud, Joëlle. "Impact of the UPR pathway on the establishment of the senescent phenotype induced by UVB." Electronic Thesis or Diss., Université de Lille (2022-....), 2024. http://www.theses.fr/2024ULILS036.
Full textSkin ageing, influenced by a combination of intrinsic and extrinsic factors, can result in damage that has the potential to alter skin functions. Among extrinsic factors, ultraviolet (UV) radiation is responsible for skin photoageing. These factors notably contribute to the accumulation of senescent cells which in turn can contribute to the development of age-related pathologies, including skin cancers. Indeed, senescence is characterized by profound morphological and molecular changes within the cell. This includes a modification of its secretome, which becomes enriched in pro-inflammatory cytokines, growth factors, and matrix-remodelling enzymes, altering tissue characteristics during ageing. However, the exact mechanisms driving the senescent phenotype induced by UVB remain largely unknown. In this context, the main objective of this work was to identify the underlying molecular mechanisms responsible for the establishment of UVB-induced senescence in normal human dermal fibroblasts (NHDFs), mechanisms that may play a role in skin ageing. In vitro, we confirmed that repeated exposures to UVB induce premature senescence of NHDFs and that this state is associated with the activation of the three branches of the Unfolded Protein Response (UPR), which are responsible for maintaining endoplasmic reticulum (ER) homeostasis, the primary cellular secretion compartment. These observations were supported by transcriptomic analysis, revealing regulatory elements related to major senescence pathways and ER functions in UVB-exposed NHDFs. Subsequently, we demonstrated that the ATF6α branch plays a central role in the development of the UVB-induced senescent phenotype. Indeed, the silencing of ATF6α not only protects against morphological changes induced by UVB, but also reduces the percentage of senescence-associated β-galactosidase (SA-βgal) positive cells, prevents the persistence of DNA damage, and alters the expression of major factors associated with the senescence-associated secretory phenotype (SASP). The SASP, exerting a pro-tumoral action, led us to assess whether the conditioned medium (CM) from UVB-exposed fibroblasts invalidated for ATF6α could impact the migration and invasion potential of melanoma cells. However, we did not observe any ATF6α-dependent pro-migratory or pro-invasive effects. To highlight a potential role of ATF6α in another biological process, we further analyzed our transcriptomic and secretomic analyses and identified a possible effect of ATF6α on the paracrine control of the skin environment. To explore this, we focused on SASP factors (cytokines and metalloproteinases) regulated by ATF6α and whose impact on tissue environment was known. Subsequently, we treated a reconstructed human epidermis (RHE) model with CM from NHDFs exposed or not to UVB and invalidated or not for ATF6α.Surprisingly, we observed that the CM from UVB-exposed NHDFs increased the thickness of the RHE as well as the proliferation of basal keratinocytes, via an ATF6α-dependent mechanism. Finally, we identified IL-8 as a major paracrine factor involved in this process, as blocking IL-8 with neutralizing antibodies prevented excessive proliferation of keratinocytes. In conclusion, we report the role of ATF6α in UVB-induced senescence and its impact on the preservation of skin homeostasis under stress conditions, particularly through the regulation of the expression of SASP components. This suggests that ATF6α and its effectors could be promising targets for controlling the effects of skin ageing
Grandjean-Laquerriere, Alexia. "Mécanismes de régulation de la production de cytokines pro-inflammatoires (TNF-α,IL-6,IL-)8 et IL-18 et anti-inflammatoire (IL-10) : modèle du kératinocyte humain irradié par des UVB/Alexia Grandjean." Reims, 2001. http://www.theses.fr/2001REIMP202.
Full textMeisse, Delphine. "Glutamine, gonflement cellulaire et régulation de l'expression du gène de l'alpha 2-macroglobuline dans le foie de rat." Rouen, 1999. http://www.theses.fr/1999ROUES076.
Full textGautheron, Jérémie Francis Alexis. "Les processus d’ubiquitination dans la voie de signalisation NF-kB et leurs dérèglements en pathologie." Paris 5, 2011. http://www.theses.fr/2011PA05T052.
Full textThe NF-kB signaling pathway plays a key role in inflammation, immune response and protection against apoptosis. Its activity is controled by IKK, a kinase complex which is composed of two catalytic subunits (IKK1/IKK2) and one regulatory subunit (NEMO). It has been reported that intricate ubiquitination processes, still poorly defined, regulate the activity of IKK and involve NEMO. During this work, we have tried to define in more details the role of NEMO ubiquitination in the activation process of IKK and how it is controled by the E3 ubiquitin ligase TRAF6. A molecular analysis of NEMO mutations causing the genetic disease Incontinentia Pigmenti (IP) has been carried out. This has allowed us to identify the interaction domains between NEMO and TRAF6, to get insights into the defects causing IP and, exploiting the data concerning the NEMO/TRAF6 interface, to propose a new strategy to modulate the NF-kB activation process
Harroch, Sheila. "Les facteurs de transcription impliqués dans l'action de l'interleukine-6." Toulouse 3, 1994. http://www.theses.fr/1994TOU30211.
Full textHamard, Pierre Jacques. "Contribution à l'étude du facteur de transcription ATF7." Université Louis Pasteur (Strasbourg) (1971-2008), 2005. https://publication-theses.unistra.fr/restreint/theses_doctorat/2005/HAMARD_Pierre_Jacques_2005.pdf.
Full textATF7 proteins, which are members of the b-Zip family of transcription factors, are able to bind ATF/CRE sequences (TGACGTCA) within different early adenoviral or cellular promoters. ATF7 can interact with the family of Jun/Fos oncoproteins and modulate their activities. To get an insight into the transactivation mechanism mediated by ATF7, we analyzed its relations with hsTAFs proteins, which are components of several multiproteic complexes like TFIID. Our results show that transactivation by ATF7 is specifically mediated by hsTAF12, mainly by its 20-kDa isoform. Moreover, ATF7 and hsTAF12 interact in vivo : the integrity of the ATF7 amino-terminal activation domain and of the hsTAF12 "histone-fold" domain is required for this interaction. We show that hsTAF12 mediated transactivation is specifically inhibited by hsTAF4 (its heterodimerization partner within TFIID), and not by hsTAF4b, a tissue-specific hsTAF4 homolog. Ubc9, a protein involved in the SUMOylation pathway, was found among the proteins interacting with ATF7 and modulating its activity. We have identified a consensus SUMOylation site within the N-terminal part of ATF7 and demonstrate that ATF7 is SUMOylated both by in vitro and in vivo experiments. Moreover, our results reveal that the intracellular localization of ATF7 is affected by its SUMOylation : ATF7 is found in the nucleus only in a de-SUMOylated form ; the cytoplasmic SUMOylation of ATF7 likely induces its sequestration at the level of the nuclear pore complexes (NPC). Using immunohistochemistry assays, we observe a colocalization between ATF7 and RanBP2, a protein of the NPC, which is an E3 ligase of the SUMOylation pathway. Accordingly, RanBP2 is able to stimulate ATF7 SUMOylation in vitro. This NPC targeting seems to influence ATF7 transactivation activity as an ATF7 mutant, whose SUMOylation is impaired, is more active than its SUMOylated counterpart. These results correlate with our chromatin-immunoprecipitation (ChIP) experiments, which show that the occupancy of a target promoter by ATF7 is highest in the presence of the unSUMOylated protein
Corvaisier, Matthieu. "Implication des co-activateurs transcriptionnels YAP/TAZ dans la régulation entre la croissance et la dormance tumorale des cellules du cancer colorectal : mécanismes moléculaires et perspectives thérapeutiques." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S028/document.
Full textColorectal cancer is the most frequent and lethal cancerous pathology from the digestive system. Each year in France, 41 000 new cases are diagnosed and 17 000 patients die due to this pathology. This high mortality is mainly due to the rate of patients with liver metastatic lesions and the early relapse of those metastases after treatment. The use of chemotherapy prior to surgery induces a decrease of early relapse, however 2 years after resection this advantage is lost. Thus, understanding the mechanisms underlying escape to treatment is required to try to delay or prevent tumor recurrence.The aim of this doctoral work was to analyze clonal chemoresistant subpopulations derived from the colorectal cancer cell line HT29 after chronic exposure to 5-Fluorouracil (5FU) and molecular mechanisms associated with chemoresistance. The most chemoresistant clonal subpopulation, 5F31, stops its proliferation after treatment with high dose of 5FU, this behavior being associated with the modulation of the c-Yes/YAP axis. After treatment, 5F31 cells enter quiescence, interaction between c-Yes and YAP is lost and total and nuclear YAP protein expression reduces significantly (Igoudjil, Touil, Corvaisier et al. 2014, Clinical Cancer Research). The next step was to study functions of YAP protein in this chemotherapy- induced quiescence.Pharmacological or transient inhibition of YAP and its homolog TAZ, induces quiescence and reduces cellular growth in several colorectal cancer cell lines. On the other hand, overexpression of a constitutively active form of YAP in 5F31 cells forces cells to remain proliferative under 5FU treatment, enhancing 5F31 cell chemosensitivity to 5FU.Regarding proteic effectors, quiescence (either induced by 5FU or YAP/TAZ inhibition) is associated with loss of expression of the transcription factor c-Myc and Cyclin E1. In 5F31 cells expressing the active mutant form of YAP, Cyclin E1 expression is sustained after 5FU treatment through the activation of the transcription factor CREB. Cyclin E1 inhibition is sufficient to induce quiescence, therefore introducing this protein as one of the final effectors of YAP/TAZ co-activators in the regulation of the proliferation/quiescence switch in colorectal cancer cells (Corvaisier et al. 2016, Oncotarget).To conclude, our work reveals the importance of YAP/TAZ proteins for the maintenance of colorectal cancer cells proliferation through Cyclin E1 expression. Our work on liver metastases from patients with colorectal cancer shows that high expression of YAP/TAZ is connected to a higher proliferative index in metastatic lesions. Moreover, high YAP/TAZ expression is associated with shorter patient progression-free survival and shorter overall survival. Studying the expression and level of YAP/TAZ activation could be an interesting prognosis marker to anticipate metastatic relapse and potent druggable target to delay tumoral recurrence
DE, GRAEVE FABIENNE. "Etude de differents partenaires du facteur de transcription atfa." Université Louis Pasteur (Strasbourg) (1971-2008), 1999. http://www.theses.fr/1999STR13089.
Full textYu, Vionnie Wing Chi. "Factor inhibiting ATF4-mediated transcription is a novel leucine zipper transcriptional repressor that regulates bone mass." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103311.
Full textSu, Ling-I. "The effects of disease mutations on the transcription factor Interferon Regulatory Factor 6." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/the-effects-of-disease-mutations-on-the-transcription-factor-interferon-regulatory-factor-6(62a14772-f8c5-45f8-84ca-c9d9320fa93b).html.
Full textBronchain, Odile. "Molecular cloning and characterization of the rat GATA-6 transcription factor." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0023/MQ50729.pdf.
Full textBronchain, Odile. "Molecular cloning and characterization of the rat GATA-6 transcription factor." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=20298.
Full textDavies, Andrew James. "The structure and function of the human transcription factor GATA-6." Thesis, King's College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326236.
Full textDiring, Jessica. "Mécanismes moléculaires de la régulation fonctionnelle du facteur de transcription ATF7." Strasbourg, 2010. https://publication-theses.unistra.fr/restreint/theses_doctorat/2010/DIRING_Jessica_2010.pdf.
Full textATF7 transcription factor is a member of the b-Zip family that heterodimerizes with Jun/Fos oncoproteins, binds to CRE (cAMP response element) or TRE (TPA response element) promoter elements and regulates the expression of specific cellular and viral genes. This study leads to a better insight into the molecular mechanisms involved in the regulation of ATF7 transcriptional activity. Phosphorylation and sumoylation are post-translational modifications that are implicated in this control by targeting the activation domain of the protein. Our results indicate that upon EGF stimulation, ATF7 gets phosphorylated by p38-bêta2 MAP kinase, which promotes its interaction with the transcription preinitiation complex, leading to the activation of gene expression. We also identified and characterized a new short alternatively spliced variant of ATF7 encoding a cytoplasmic protein, ATF7-4. The latter is highly conserved amongst mammalian species and regulates the activity of ATF7 and its paralog ATF2 under non-stressed conditions by retaining in the cytoplasm a kinase that is essential for their activity. ATF7-4 degradation is a prerequisite for the release of this kinase and the subsequent activation of ATF7/2 under stressed conditions. To decipher the cellular function of ATF7, we finally initiated a genome wide mapping of its target genes by a ChIP-seq technology. Our results indicate that ATF7 could regulate multiple key cellular pathways, especially cell division, signaling and metabolism, and may play a crucial role in cell homeostasis
Batnini, Kalil. "Rôles de la protéine E4F1 dans le contrôle de la réponse aux dommages de l’ADN dans le cancer du sein triple négatif." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT003.
Full textThe E4F1 protein discovered as the cellular target of the adenoviral oncoprotein E1A is a ubiquitous protein acting both as a transcription factor and as an atypical E3-ligase. E4F1 protein also interacts directly with several cellular tumor suppressors and oncoproteins, suggesting its involvement in tumorigenesis. Previous laboratory work on the cellular functions of E4F1 in cancer cells has shown that its depletion leads to massive cell death in transformed Mefs deficient in p53. In addition, E4F1 directly controls the expression of 38 genes, including genes involved in cell metabolism and cell cycle checkpoints/DNA Damage Response (DDR), such as Chek1 that encodes a major component of the ATR/ATM checkpoint. Consistent with this role of E4F1 in cancer cell survival in mice, patients with triple-negative breast cancer (TNBC) with high E4F1 expression exhibit a poorer relapse free survival (RFS).We therefore aimed to study for the first time the transcriptional program of E4F1 in human cells and explore its role in the survival of TNBC cells, with particular focus on its role in the response to chemotherapy agents.Transcriptomes (RNAseq) of SUM159 TNBC cells show, when E4F1 is depleted, a decrease in expression of 147 out of 276 DDR-associated genes. The combination of RNAseq and ChIPseq shows that E4F1 directly regulates 57 genes in human TNBC cells. Among these genes, E4F1 itself, CHEK1, but also TTI2 and PPP5C coding for post-transcriptional regulators of the ATM/ATR-CHK1 axis, and thus defining an ATM/ATR-CHK1 "regulon", undescribed and E4F1-dependent. TTI2 composes with TELO2 and TTI1, the TTT complex required for the correct folding and stability of PIKK family proteins, such as ATR and ATM. PPP5C phosphatase is involved in the activation of ATR-CHK1 signaling. Importantly, we show that E4F1 binds to and probably regulates these three genes in vivo in Patient Derived TNBC Xenografts (PDTX). In both SUM159 cells and PDTX, the recruitment of E4F1 on these genes is increased upon Gemcitabine treatment, a chemotherapy agent that impairs DNA replication. Surprisingly, we found that E4F1 also indirectly controls the expression of TELO2, a second member of the TTT complex. Consequently, in TNBC cells depleted of E4F1, the protein levels of CHK1, TTI2, TELO2 but also ATM/ATR kinases, are significantly decreased, leading to DDR deficiency. Thus, SUM159 cells depleted of E4F1 fail to stop in phase S during Gemcitabine treatment and are highly sensitized to this chemotherapy agent, as well as other DNA damaging agents such as Cisplatin. Altogether, my thesis results demonstrate that the ATM/ATR-CHK1 signaling pathway, and the response to stress / DNA damage are tightly controlled at the transcription and post-transcription levels by E4F1. E4F1 therefore appears to be a central actor in the cellular survival of TNBC cells, particularly when exposed to DNA-damaging agents or chemotherapy agents. Thus, E4F1 could represent a prognostic marker for chemotherapy response and a potential therapeutic target
LIU, CONG. "REGULATION OF LUNG EPITHELIAL DIFFERENTIATION ALVEOLARIZATION AND GENE EXPRESSION BY GATA-6 IN VITRO AND IN VIVO." University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1026498687.
Full textJadhav, Kavita Jadhav. "Hepatic Activating Transcription Factor 3 (ATF3) in Lipid Metabolism." Kent State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=kent1511806289848847.
Full textZazzi, Henric. "Human insulin-like growth factor binding protein -4 and -6 : gene structure and transcription regulation /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-3873-3/.
Full textSansó, Martínez Miriam. "Role of the stress-dependent MAP kinase Sty1 and the transcription factor Atf1 in transcription regulation in fission yeast." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/22698.
Full textEn Schizosaccharomyces pombe, la vía de la MAPK Sty1 es activada ante diferentes situaciones de estrés, como son el estrés oxidativo u osmótico, fase estacionaria, radiación UV o choque de calor. Al ser la modulación de la expresión génica uno de los más importantes objetivos de esta respuesta, hemos focalizado el trabajo de esta Tesis doctoral en la caracterización de la regulación transcripcional mediada por la activación de la ruta de Sty1 y los factores de transcripción Atf1 y Pcr1. Además, hemos ampliado nuestra área de interés investigando el papel de remodeladores de cromatina relacionados con la respuesta a estrés y cómo a participan en la transcripción estrés-dependiente.
Apra, Caroline. "Etude du développement des méninges & modélisation de tumeurs fibreuses solitaires chez la souris par introduction du gène de fusion NAB2-STAT6 dans les cellules PGDS-positives." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL052.
Full textMeningeal solitary fibrous tumors (SFT), like somatic SFT, are characterized by the NAB2-STAT6 fusion gene. This fusion induces the nuclear relocation of the STAT6 transcription factor and the activation of EGR transcription, increasing proliferation. Meningeal SFT cells, like meningioma cells, are positive for prostaglandin-D2-Synthase (PGDS), a specific marker of meningeal, especially arachnoid, cells. In Part 1, we showed that benign SFT can transform into malignant TFS - formerly hemangiopericytomas - and we reported the therapeutic efficacy of pazopanib, an inhibitor of vascular endothelial growth factor. Part 2 is devoted to the molecular study of SFT: the comparison of the exome of pairs of SFT, a grade I primary and grade III recurrence, brought out the pathogenic variant of TP53 c.743G> T. The transcriptome of meningeal SFT showed the aggregation of SFT from all localizations, distinct from meningiomas. Part 3 presents the modeling of meningeal SFT in genetically modified mice by the introduction of two NAB2-STAT6 fusion genes (exons 2-16 and 6-17). The RCAS-NAB2-STAT6 retroviruses, injected at birth into the subdural space of PGDS-tva mice, specifically infect arachnoid cells. After more than a year of follow-up, the animals did not develop any SFT. It is likely that, as in many other tumor models, fusion is not sufficient to induce tumor development. In Part 4, we adapted the iDisco method, which usually allows three-dimensional visualization of brain samples, for mouse embryos and whole skulls, and described the expression of PGDS in mice in situ, between the 11th post-conception day and the 7th post-natal day. It is located in the meninges at the skull base in the early stages and at the convexity after birth, and also in the radial glia
Crutchfield, Gerald L. "Kruppel-Like Transcription Factor 6 & 7 mRNAs (KLF6 & KLF7) Expression in the Developing Zebrafish." University of Akron / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=akron1572200378181869.
Full textPASINI, SILVIA. "Role of activated transcription factor 4 (ATF4) in learning and memory." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2011. http://hdl.handle.net/10281/27132.
Full textLanglois, Marie-Claire. "Contribution à l'étude de la fonction et de l'évolution de deux facteurs de transcription PAX-6 et COUP-TF." Lille 1, 1998. https://pepite-depot.univ-lille.fr/LIBRE/Th_Num/1998/50376-1998-443.pdf.
Full textSt, Germain Carly. "The Role of Activating Transcription Factor 3 (ATF3) in Chemotherapeutic Induced Cytotoxicity." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20000.
Full textBrown, Andrew Dickson. "Identification and analysis of alternative aberrant forms of the transcription factor ATF1." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244185.
Full textMalabanan, Kristine Paz Centre for Vascular Research Faculty of Medicine UNSW. "Roles of activation transcription factor 4 (ATF4) and YrdC in the response of vascular smooth muscle cells to injury." Publisher:University of New South Wales. Centre for Vascular Research, 2008. http://handle.unsw.edu.au/1959.4/41338.
Full textPaulo, Mirasol Esther 1984. "Regulation of gene expression program by the MAPK Sty1 and the transcription factor Atf1." Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/382838.
Full textEls radicals lliures d’oxigen (ROS) són unes molècules derivades de l’oxigen provinents de diferents processos metabòlics. ROS poden reaccionar amb diferent components cel•lulars, resultant en peroxidació d’àcids grassos, oxidació de proteïnes i danys al DNA. Els organismes unicel•lulars estan sotmesos a una àmplia varietat de canvis ambientals i a l’exposició de compostos tòxics. En resposta a l’estrés oxidatiu provocat pel peròxid d’hidrogen, S. pombe activa diferent vies de senyalització segons la severitat de l’estrés sofert, dut a terme per dos factors de transcripció, Pap1 i el bZIP Atf1 sota el control aquest últim de la MAPK. En el llevat S. pombe, Pap1 i Sty1 constitueixen un paper clau per lat resposta a l’estrés oxidatiu. La MAPK Sty1 s’activa sota l’efecte de diferent estressos, aixi com l’estrés oxidatiu o l’osmòtic. La modulació de la resposta gènica és un dels principals punts en aquesta resposta, hem centrat el treball d’aquesta tesis en la caracterització de la ruta de Sty1 com a sensor de l’estrés oxidatiu així com els diferents events moleculars que activen el programa transcripcional. També hem estudiat el paper de la traducció per l’Elongato en la inducció de la resposta a estrés.
Hasim, Mohamed Shaad. "The Role of Activating Transcription Factor 3 as a Regulator of DNA-Damaging Chemotherapy Cytotoxicity." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39897.
Full textPietro, Luciana 1981. "Expressão dos fatores LIF (Fator Inibitório de Leucemia), IL-6 (Interleucina-6), STAT-3 (Ativador de Transcrição-3) e telomerase em coriocarcinomas." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310449.
Full textTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A invasão do endométrio pelo trofoblasto extraviloso é fundamental no desenvolvimento do feto e da placenta, processo este controlado por fatores ligados à atividade imunológica e hormonal que, quando alterada, pode resultar em interrupção da gestação e/ou geração das chamadas doenças trofoblásticas gestacionais. Em algumas situações, pode haver evolução para o coriocarcinoma, neoplasia maligna do trofoblasto, em que há evidências da atuação das moléculas ligadas ao processo de fusão celular e inflamação. Porém, os estudos neste tema são incipientes e inconclusivos. Considerando essas informações, o objetivo deste trabalho é estudar de forma comparativa a expressão das citocinas LIF, IL-6 e do ativador de transcrição STAT-3, além da telomerase, em material de aborto, de placenta normal a termo e de coriocarcinoma. Métodos: a expressão destas moléculas foi avaliada pelos métodos: imunoistoquímica (IHQ), imunofluorescência (IF), Western Blotting (WB) e Real-Time PCR (RT-PCR), em amostras de material de aborto, placenta normal a termo e coriocarcinoma (N=12 cada um). Os ensaios de WB e Real-Time PCR empregaram material a fresco de placenta normal a termo e seu cultivo celular e cultura da linhagem BeWo. Resultados: no material de aborto, as reações de IHQs evidenciaram expressão moderada de IL-6 em 58,4% dos casos e intensa de STAT-3 em 33,3%. Na placenta normal, observou-se intensa marcação de IL-6 em 50% e de STAT- 3 em 16,7% dos casos, enquanto que, no coriocarcinoma, houve expressão intensa de IL-6 em 50% e de STAT-3 em 75% dos casos. Por outro lado, as reações para LIF tiveram expressão nula em todos os três grupos. Pelo WB houve expressão proteica de IL-6 apenas no material fresco de placenta normal e ausência de expressão na sua cultura primária e na linhagem BeWo; LIF não foi expresso em todos os grupos estudados. STAT-3 foi detectado no citoplasma em todos os grupos, entretanto, a expressão nuclear da STAT-3 fosforilada (pSTAT-3) não foi observada na IF e nem pelo WB. Na análise gênica pelo RTPCR houve forte expressão de IL-6 e STAT-3 no material fresco de placenta normal e expressão muito fraca na cultura primária de placenta normal e na linhagem BeWo; a expressão de LIF foi muito fraca em todos os grupos. Apenas a linhagem BeWo demonstrou forte expressão gênica da telomerase, contrastando com a completa falta de expressão no material fresco de placenta normal e em sua cultura primária. Conclusão: A intensa expressão IHQ de IL-6 e STAT-3 no coriocarcinoma indica a atuação de ambas na carcinogênese. A expressão proteica de IL-6 no material fresco de placenta normal e sua ausência no material de cultura primária e na linhagem BeWo pode ser ocasionado pelo contato célula-a-célula nas culturas aderentes, inibindo o crescimento celular e, consequentemente, as vias de sinalização. A falta de expressão da pSTAT-3 tanto na IF como por WB demonstra que a via JAK-STAT está sendo desativada. A ausência de expressão de LIF, em todos os métodos estudados, sugere que esta citocina poderia estar sendo inibida por meio de proteínas SOCS3 ou, atuando, de modo indireto, na proliferação celular do coriocarcinoma. O aumento da atividade da telomerase nas células BeWo reforça sua relação com o fenótipo maligno e a aponta como um bom marcador para progressão da doença
Abstract: The invasion of the endometrium by extravillous trophoblast is a fundamental process in the growth of the fetus and placenta. The process is controlled by factors related to the immune and hormonal activity that, when changed, may result in termination of pregnancy and development of so-called gestational trophoblastic diseases. In some cases, changes can result in malignancy, in which some molecules play a role in cell fusion process and inflammation, although studies in this area are inconclusive. Considering this information, the study had the aim of investigating the expression of cytokines LIF, IL-6, STAT- 3 and the function of telomerase to understand their participation in abortion, in normal at term placenta and choriocarcinoma. Methods: The expression of the molecules was assessed by immunohistochemical assay (IHC), immunofluorescence (IF), Western Blotting (WB) and Real-Time PCR (RT - PCR) using fixed material from biopsies of abortions, normal at term placentas and choriocarcinoma along with fresh tissue of normal at term placenta and their primary culture and BeWo cell line. Paraffin embedded material used in IHC and IF assays were obtained from the Department of Pathology files. Tests of WB and Real-Time PCR employed fresh material, obtained from cell cultures of normal at term placenta and the BeWo line. Results: IHC reactions to abortion biopsies showed moderate staining for IL-6 in 58.4% of cases and intense for STAT-3 in 33.3 % of cases. In biopsies of normal placenta, there was intense reaction for IL-6 in 50% of cases, intense for STAT-3 in 16.7%; choriocarcinoma showed intense staining for IL- 6 in 50% of cases and also for STAT-3 in 75% of cases. On the other hand, LIF expression was missing in all three groups. WB analyses showed IL-6 protein in fresh material from normal placentas, but no expression in placenta primary cultures and BeWo line. LIF was absent in all groups. Cytoplasmic STAT-3 was observed in all groups, while the nuclear expression of phosphorylated STAT-3 was absent. On gene analyses a strong expression of IL-6 and STAT- 3 was observed from fresh normal placenta, but very weak expression in primary cultures of normal placenta and BeWo cell line. LIF expression was very weak in all groups. In regard to the gene expression of telomerase, it was strong in the BeWo line which contrasted with its complete lack of expression in fresh normal placenta and its primary culture. Conclusion: The high expression of IL-6 and STAT-3 in biopsies of choriocarcinoma indicates the role of both in tumor progression. Regarding protein expression, the presence of IL-6 in the material from fresh normal placenta, and its absence in primary culture and BeWo line may be caused by the cell-to-cell contact cultures by inhibiting cell growth and thus signaling pathways. However, the lack of expression of phosphorylated STAT-3 whether through IF or WB shows that its JAK-STAT pathway is inhibited. Lack of expression of the LIF suggests that it might be involved indirectly in choriocarcinoma cell proliferation or be inhibited by SOCS3 protein. Moreover, the increased telomerase activity of BeWo cells enhances their relation to the malignant phenotype and indicates a good marker for disease progression
Doutorado
Ciencias Biomedicas
Doutora em Ciências Médicas
Li, Wenzhao. "A homeobox protein, NKX6.1, up-regulates interleukin-6 expression for cell growth in basal-like breast cancer cells." Kyoto University, 2016. http://hdl.handle.net/2433/216184.
Full textVincent, Sylvie. "Intérêts des gènes à homéodomaines PAX-6 et Engrailed-2 dans le diagnostic et le pronostic des tumeurs neuroectodermiques primitives humaines." Lille 1, 2003. https://ori-nuxeo.univ-lille1.fr/nuxeo/site/esupversions/cdf25b11-a440-48c3-866f-6005820f1805.
Full textKlotz, Rémi. "Rôle de la protéine Damaged DNA Binding 2 dans la réponse des cellules tumorales mammaires aux agents thérapeutiques." Thesis, Université de Lorraine, 2014. http://www.theses.fr/2014LORR0134/document.
Full textThe laboratory has recently identified the Damaged-DNA Binding 2 protein (DDB2), a protein involved in DNA repair, as an important actor in breast tumorigenesis. Our laboratory has shown that DDB2 is involved in breast tumor growth and progression through the transcriptional regulation of target genes. Thus, the first aim of this work was to study the role of DDB2 and its target genes in the response of breast cancer cells to anticancer drugs. We showed that DDB2 overexpressed in breast cancer cell lines, such as MDA-MB231 and SKBr3, increased the cells sensitivity to apoptosis induced by doxorubicin and 5-Fluorouracil (5-FU). Conversely, the inhibition of DDB2 expression in T47D cells, which express endogenously this protein, decreased cell sensitivity to anticancer agents. Our results showed that cell sensitivity induced by DDB2 expression to 5-FU but not doxorubicin depended on its ability to repress NF-κB activity via the regulation of IκBα expression. At last, the search of potential DDB2 target genes implicated in apoptosis has led us to identify the anti-apoptotic factor Bcl-2. We showed the ability of DDB2 to downregulate Bcl-2 expression via its interaction with DNA region located in P2 promoter of the corresponding gene. Results suggest that Bcl-2 dowregulation by DDB2 could be a major event that explains the enhanced sensitivity of cancer cells to therapeutic agents. Altogether, these data highlight the clinical interest of DDB2, as a predictive marker of the response to anticancer agents. A better understanding of its mode of action will contribute to improve therapeutic treatments and avoid their failure in resistant patients
Enikanolaiye, Adebola. "The Role of the Claudin 6 Cytoplasmic Tail In Epidermal Differentiation and the Role of Cdx In Endodermal Development." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32354.
Full textWolford, Christopher C. "The roles of ATF3, an adaptive-response gene, in cancer development and metastasis." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1267123304.
Full textGRIGOLATO, Jessica. "ACTIVATING TRANSCRIPTION FACTOR 4 (ATF4) IS UPREGULATED BY HUMAN HERPESVIRUS 8 INFECTION, INCREASES VIRUS REPLICATION AND PROMOTES VIRUS PROANGIOGENIC PROPERTIES." Doctoral thesis, Università degli studi di Ferrara, 2013. http://hdl.handle.net/11392/2388888.
Full textPersson, Emma. "The Neuropeptide VIP and the IL-6 family of cytokines in bone : effects on bone resorption, cytokine expression and receptor signalling in osteoblasts and bone marrow stromal cells /." Doctoral thesis, Umeå : Umeå University, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-606.
Full textChan, Shing Fai. "ATM phosphorylates and activates the transcription factor MEF2D for neuronal survival in response to DNA damage." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3359980.
Full textTitle from first page of PDF file (viewed July 22, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 73-92).
Brenner, Carmen. "Le rôle des méthyltransférases de l'ADN dans la régulation transcriptionnelle." Doctoral thesis, Universite Libre de Bruxelles, 2005. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211114.
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Doctorat en sciences biomédicales
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Luo, Songjiang. "Regulation of isoform-specific sodium channel expression at nodes of Ranvier /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
Find full textTypescript. Includes bibliographical references (leaves 125-138). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;