Tesis sobre el tema "ATF6α"
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Forouhan, Mitra. "The role of ATF6α and ATF6β in the UPR associated with an ER stress-induced skeletal chondrodysplasia". Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-atf6alpha-and-atf6-in-the-upr-associated-with-an-er-stressinduced-skeletal-chondrodysplasia(9e26ce51-f188-454c-8ee1-3832845ee014).html.
Texto completoEgawa, Naohiro. "The endoplasmic reticulum stress sensor, ATF6α, protects against neurotoxin-induced dopaminergic neuronal death". Kyoto University, 2011. http://hdl.handle.net/2433/142092.
Texto completoGiroud, 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.
Texto completoSkin 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
Felden, Julia Verfasser] y Bernd [Akademischer Betreuer] [Wissinger. "Die Bedeutung von Atf6 für die Zebrafischretina : Generierung und Charakterisierung eines atf6-/- - Zebrafischmodells / Julia Felden ; Betreuer: Bernd Wissinger". Tübingen : Universitätsbibliothek Tübingen, 2019. http://d-nb.info/1199929522/34.
Texto completoSICARI, DARIA. "Unveiling a role for mutant p53 in regulation of Unfolded Protein Response". Doctoral thesis, Università degli Studi di Trieste, 2018. http://hdl.handle.net/11368/2924770.
Texto completoSantinelli, Raphaël. "Inhibition de la voie ATF6 de la réponse aux protéines mal formées comme nouvelle approche thérapeutique dans le cadre de la mucoviscidose". Electronic Thesis or Diss., Brest, 2024. http://www.theses.fr/2024BRES0009.
Texto completoCystic fibrosis is the most common lethal autosomal recessive genetic disease in the European population. It is caused by mutations in the CFTR gene, the most common of which is the deletion of a phenylalanine at position 508 of the protein's polypeptide sequence (p.Phe508del- CFTR). These mutations alter the viscosity of the mucus present on the apical surface of epithelial cells in the respiratory, digestive and genital systems. This leads to a reduction in mucociliary clearance, making it difficult to renew the mucus that forms the first protective barrier against the development of potentially pathogenic micro- organisms. As a result, inflammatory and infectious responses are triggered. By adding the accumulation of misfolded proteins in the lumen of the ER, the UPR adaptive defence mechanism is triggered. ATF6 is one of its three regulatory pathways. ATF6 has been shown to inhibit CFTR expression. The aim of this thesis project is to evaluate the effects of inhibiting S1P, a protein central for the activation of ATF6, on p.Phe508del-CFTR by pharmacological means. The results show that Cl- ion efflux linked to the activity of the p.Phe508del-CFTR channel is increased through an increase in the overall expression and transport of this channel to the plasma membrane. We also give some possible explanations for these beneficial effects, in particular in relation to the triggering of the UPS, a pathway that allows mutated proteins to be transported to the plasma membrane
Huguet, Florentin. "Impact de la modulation de TRPM7 et ATF6 sur le cystic fibrosis transmembrane conductance regulator". Thesis, Brest, 2017. http://www.theses.fr/2017BRES0058/document.
Texto completoCystic fibrosis is caused by mutations in the cftr gene resulting in several defaults on the CFTR protein. The most frequent mutation is F508del which is characterized by an incorrect folding causing its retention within the ER. CFTR-F508del protein accumulation in the ER, inflammation and infections will trigger the ER stress in epithelial cells, as well as UPR. UPR constitutes an adaptive response of the ER in order to restore ER’s homeostasis. UPR consists in three major pathways. Among them, one is activated in cells expressing CFTR-F508del protein. The ATF6 pathway of UPR is responsible of the transcriptional repression of CFTR, which makes of it a potential therapeutic target. We showed that the inhibition of ATF6 leads to the improvement of CFTR-508del function, as well as its increased presence in the cellular membrane. We were also interested in Mg2+ and TRPM7, the main regulator of [Mg2+]i. We suspected that TRPM7 is, at least in part, responsible for the activation of ATF6 in cells expressing the mutant CFTR-F508del. Thus, the second part of my work was focused on the study of the relationship between Mg2+, TRPM7 and CFTR. We showed the existence of [Mg2+]I differences according to CFTR mutant expressed in cells. These differences are the result of an altered TRPM7 activation, probably in link with the mutated CFTR’s malfunction. We proved that increasing TRPM7 activity by Naltriben treatment potentiates CFTR-G551D
Papaioannou, Alexandra. "Fine-tuning UPR signals and subsequent cellular outputs". Thesis, Rennes 1, 2019. http://www.theses.fr/2019REN1B013.
Texto completoThe present thesis explores the world of ER (endoplasmic reticulum) stress biology. A global view of ER and ER stress is first provided with a transition from the basic mechanisms involved to possible clinical applications. The focus is then placed to the crucial role of the UPR in carcinogenesis that is activated in response to ER stress in the micro-environment of the tumor. After reviewing these aspects, we point to missing parts in our comprehension of how UPR signals are fine-tuned and lead to either restoration of ER and cell homeostasis or cell death. Among the UPR branches, ATF6 and IRE1 signaling become our focus of investigation because of their convergence in the regulation of the pro-survival factor XBP1s. On the one hand, we unravel mechanisms originating from the ER lumen that regulate the ATF6 activation in response to ER stress and affect its downstream cell adaptive signaling. On the other hand, we witness the existence of an auto-regulatory network of IRE1 RNase activity consisted of a tyrosine kinase-phosphatase system that targets RtcB and impacts on XBP1 mRNA splicing. Hence, through our studies we uncover an integrated signaling circuit that can fine-tune the cellular outputs of the joint ATF6 and IRE1 activation in response to ER stress
Martindale, Joshua J. "Protecting the myocardium from ischemia and reperfusion injury via inducible activation of ATF6 or constitutive expression of MKK6 /". Diss., Connect to a 24 p. preview or request complete full text in PDF formate. Access restricted to UC campuses, 2006. http://wwwlib.umi.com/cr/ucsd/fullcit?p3236641.
Texto completoLyle, Chimera. "Super Low Dose Endotoxin Exacerbates Low Grade Inflammation through Modulating Cell Stress and Decreasing Cellular Homeostatic Protein Expression". Diss., Virginia Tech, 2017. http://hdl.handle.net/10919/86360.
Texto completoPh. D.
Baier, Katrin Maria [Verfasser]. "Modulation der Unfolded Protein Response (UPR) bei Überexpression der Hepatitis-B-Oberflächenantigene unter Berücksichtigung des Transkriptionsfaktors ATF6 / Katrin Maria Baier". Gießen : Universitätsbibliothek, 2018. http://d-nb.info/1173086838/34.
Texto completoBaier, Katrin [Verfasser]. "Modulation der Unfolded Protein Response (UPR) bei Überexpression der Hepatitis-B-Oberflächenantigene unter Berücksichtigung des Transkriptionsfaktors ATF6 / Katrin Maria Baier". Gießen : Universitätsbibliothek, 2018. http://d-nb.info/1173086838/34.
Texto completoDI, CRISTINO FRANCESCA. "The stress-activated kinase p38MAPK contributes to ATF6 activation and resistance to ER stress in cancer cells with mutant p53". Doctoral thesis, Università degli Studi di Trieste, 2022. http://hdl.handle.net/11368/3030938.
Texto completoNozaki, Junichi. "The endoplasmic reticulum stress response is stimulated through the continuous activation of transcription factors ATF6 and XBP1 in Ins2[+/Akita] pancreatic β cells". 京都大学 (Kyoto University), 2004. http://hdl.handle.net/2433/147911.
Texto completo古場, 玲. "ジスルフィド結合を介して構成的に形成される小胞体ストレスセンサーATF6多量体の解析". Kyoto University, 2020. http://hdl.handle.net/2433/253127.
Texto completoFu, Yanlin. "Proteostasis Maintenance of γ-aminobutyric Acid Type A Receptors (GABAARs)". Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1554993220214253.
Texto completo松居, 利江. "哺乳動物小胞体ストレス応答を制御する転写因子ATF6とXBP1の作用機作に関する研究". 京都大学 (Kyoto University), 2007. http://hdl.handle.net/2433/137023.
Texto completo堀本, 賢. "膜タンパク質小胞体ストレスセンサーATF6を基質とした小胞体関連分解因子SEL1LおよびEDEMの機能解析". 京都大学 (Kyoto University), 2016. http://hdl.handle.net/2433/215356.
Texto completoKyoto University (京都大学)
0048
新制・課程博士
博士(理学)
甲第19543号
理博第4203号
新制||理||1603(附属図書館)
32579
京都大学大学院理学研究科生物科学専攻
(主査)教授 森 和俊, 教授 阿形 清和, 准教授 細川 暢子
学位規則第4条第1項該当
Snyder, Jarin T. "ER Stress and ATF6alpha potently induce S-Phase in Old Mouse Beta Cells Cultured Ex-Vivo in High Glucose". eScholarship@UMMS, 2020. https://escholarship.umassmed.edu/gsbs_diss/1125.
Texto completo土師, 京介. "哺乳動物の小胞体ストレス応答に関与する転写調節因子ATF6の活性発現機構に関する研究". 京都大学 (Kyoto University), 2002. http://hdl.handle.net/2433/150107.
Texto completo佐藤, 吉美. "哺乳動物小胞体ストレス応答を制御する小胞体膜結合性転写因子ATF6の活性化機構に関する研究". 京都大学 (Kyoto University), 2011. http://hdl.handle.net/2433/142424.
Texto completo岡田, 徹也. "哺乳動物小胞体ストレス応答を制御する膜結合性転写因子ATF6の標的ならびに活性化プロセスに関する研究". 京都大学 (Kyoto University), 2004. http://hdl.handle.net/2433/147908.
Texto completo山本, 敬祐. "哺乳動物小胞体ストレス応答に関与するシス配列ERSE-IIの解析ならびに転写因子ATF6のターゲティングに関する研究". 京都大学 (Kyoto University), 2004. http://hdl.handle.net/2433/68781.
Texto completoLISTI', Angela. "UNRAVELLING THE ROLES OF THE NUCLEAR PROTEIN 1 DURING ER-STRESS INDUCTION". Doctoral thesis, Università degli Studi di Palermo, 2020. http://hdl.handle.net/10447/400605.
Texto completoBackground: NUPR1 was described as a transcriptional factor involved in the regulation of various cellular stress-response genes, playing a crucial role in the condition of the endoplasmic-reticulum (ER) stress, thus emerging as a common molecular factor of different pathologies, obesity, hepatic steatosis, and cancer. In the present work we aim to explore how NUPR1 interacts with some pivotal genes that are the major modulators of the ER stress and metabolic cell functions. In particular we investigated the biochemical and molecular effects arising from the loss of NUPR1 in ER stress physiological conditions. Methods: We used prolonged high fat diet (HFD) feeding to induce ER stress physiological in Nupr1+/+ and Nupr1-/- male mice compared with their respectively normal chow diet (ND) controls. We fed mice with a HFD (60% fat, 20% protein, and 20% carbohydrate) for 10 weeks to promote chronic ER stress condition (Old-HFD group, n=5). An additional group of mice (n=5) was maintained on HFD (60% fat, 20% protein, and 20% carbohydrate) for a longer duration (15 weeks) to distinguish between age-dependent and age-independent effects. Liver were collected for histological and molecular assessments. Western blots and RT-qPCR were performed to assess the expression levels of the major ER-stress response UPR-associated proteins and metabolic genes. Results: We showed the downregulation of the majority of UPR-associated proteins: BIP (p<0.0001 for protein and mRNA), ATF4 (p<0.0001 for mRNA), XBP1 (p<0.0001 for protein and mRNA), CHOP (p<0.0001 for protein and mRNA), GADD34 (p=0.0296 for mRNA) in in-vivo NUPR1-/- compared to NUPR1+/+ 10 weeks HFD mice. Western blot for the major UPR associated proteins in NURP1-/- mice at 15 weeks HFD showed similar expression trends reported at the time-point of 10 weeks. ERDj4 mRNA resulted down-regulated in NUPR1-/- compared to NUPR1+/+ 15 weeks HFD mice (p=0.0032). Among the multiple metabolic genes, we reported a down-regulation of the majority mRNA associated to lipogenesis (SREBP, ACLY, ChREBP) and lipoprotein (APOB, PPAR-alfa, MTTP) in NUPR1-/- compared to NUPR1+/ + HFD mice 15 weeks. Both LCAD and MCAD fatty acid metabolisms mRNA were also downregulated, as consequence of PPAR-alfa deficit. Similarly betaoxidation mRNA ACOX1 and CPT1-alfa, as well as MTC4 and PGK1 were downregulated in NUPR1-/- compared to NUPR1+/ + HFD mice 15 weeks. Conclusion: The results of this work confirm that NUPR1 act downstream of the PERK branch playing a crucial role of NUPR1 in the activation of UPR response in physio-pathological ER stress condition and suggest a potential contribution of NUPR1-mediated ER stress response to the development of liver steatosis.
安達, 雄亮. "哺乳動物小胞体ストレス応答を制御する小胞体膜結合性転写因子ATF6の活性化制御機構ならびに標的遺伝子に関する研究". 京都大学 (Kyoto University), 2008. http://hdl.handle.net/2433/124349.
Texto completoOrtet, Cortada Laura. "Signalling of ciclyn o complexes through EIF2alpha phosphorylation". Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7259.
Texto completoHemos identificado una nueva Ciclina, llamada Ciclina O, que es capaz de unirse y activar Cdk2 en respuesta a estímulos apoptóticos intrínsecos. Nos hemos centrado en el estudio de la Ciclina Oα y la Ciclina Oβ, productos de splicing alternativo del gen. En respuesta a diferentes tipos de estrés, la Ciclina Oα se acumula en agregaciones citoplásmicas densas que podrían corresponder a Gránulos de Estrés (SGs). Además, hemos visto que la Ciclina Oβ y un mutante puntual de la parte N-terminal de la proteína se localizan constitutivamente en los SGs. Aunque las dos isoformas alfa y beta son proapoptóticas, solo la Ciclina Oα es capaz de unirse y activar Cdk2. Por otro lado, hemos demostrado que los niveles de Ciclina O se incrementan en respuesta al estrés de Retículo Endoplásmico (RE) y que esta proteína es necesaria para la inducción de apoptosis dependiente de estrés de RE. La Ciclina O activa específicamente la vía de PERK e interacciona con la proteína inhibidora de PERK p58IPK. Además, la Ciclina O participa en la activación de otras quinasas de eIF2α. La Ciclina O se localiza en mitocondrias activas, lo que sugiere una función de la proteína ligada al metabolismo oxidativo.
Odisho, Tanya. "Investigating the Role of ATF6Beta in the ER Stress Response of Pancreatic Beta-cells". Thesis, 2013. http://hdl.handle.net/1807/43275.
Texto completoResende, Daniel Marcos da Silva. "Impact of ER stress and its reversion via chemical chaperones, on age- and proteostasis-associated pathways". Master's thesis, 2019. http://hdl.handle.net/10773/28430.
Texto completoO envelhecimento permanece até hoje uma das áreas biológicas por resolver de maior importância. Muitas doenças associadas ao envelhecimento estão a aumentar de forma global. Uma característica principal associada ao envelhecimento é a proteostase, cujos diferentes componentes ainda não foram totalmente descritos em diferentes linhas celulares. Aqui, usando um modelo celular neuronal como as células SH-SY5Y, diversos biomarcadores de stress do retículo endoplasmático e de agregação proteica foram avaliados em ambientes de stress do RE induzidos por tunicamicina ou tapsigargina, bem como a sua reversão. A inclusão de agentes protetores (TUDCA) e reversores químicos da agregação proteica (compostos HA) foram incluídos para melhor avaliar essa mesma reversão do stress do RE. BAG3, ATF4, calreticulina e pERK1/2 foram algumas das proteínas incluídas nesta dissertação e a avaliação do stress do RE foi alcançada pela análise dos seus níveis de expressão proteicos e/ou génicos. A indução do stress do RE foi alcançada eficazmente tanto para a tapsigargina como para a tunicamicina, em todas as proteínas-alvo, nesta linha celular. ATF4, calreticulina e pERK1/2 foram diminuídas pela ação dos agentes protetores e, consequentemente, diminuiu o stress do RE. No entanto, para a GRP78 e BAG3, não se obtiveram resultados de reversão do stress do RE. XBP1s apenas alcançou resultados significativos de reversão no caso das condições tratadas com tunicamicina. Em suma, o stress do RE induzido por TG ou TUN foram revertidos parcialmente ou na sua totalidade com sucesso pelos agentes protetores nesta linha celular.
Mestrado em Biomedicina Molecular
Chang, Jin-Ling y 張金鈴. "Transactivation of GRP94 by ER stress induced by GA in 9L rat brain tumor cells - Activation of the grp94 promoter mainly through ERSEs by transcription factor ATF6". Thesis, 2007. http://ndltd.ncl.edu.tw/handle/17950088837799507083.
Texto completo國立清華大學
生物科技研究所
95
Geldanamycin (GA), a benzoquinone ansamycin, is an inhibitor of heat shock protein 90 (HSP90)/ glucose-regulated protein 94 (GRP94) and has been implicated as a potent anti-cancer drug. In our previous study, we found that GA with sublethal dose provoked the ER stress in 9L rat brain tumor (RBT) cells and induced glucose-regulated proteins under unfold protein response (UPR) at transcriptional level. The promoter of grp genes contain multiple copies of the ER stress response element (ERSE), with a consensus of CCAAT(N9)CCACG, which is critical and necessary for transcription induction. Herein, we showed that GRP94, an ER resident chaperone, was induced under GA treatment in 9L rat brain tumor (RBT) cells and the mRNA level of grp94 was peaked at 8 h for about 9 fold. We analyzed the promoter sequence of grp94 according to rat genome resource and designed reporter vectors containing progressive-deleted promoters of grp94. In reporter gene assays, ERSE4 and CRE-BP1/c-Jun played the major roles in GA-induced grp94 expression. Moreover, with mutagenesis clones we further confirmed this result although other ERSEs still have involved in. By inhibitors screening, pretreatment of KT5720, BIM I, or Gö6983 partially decreased GA-induced GRP94 expression, suggesting the involvement of PKA and PKC. Pretreatment of AEBSF blocked proteolysis of ATF6 abolished GA-induced GRP94 expression. Taken together, we found that under GA induced ER stress in 9L cells, activation of GRP94 were mainly through ERSEs by the transcription factor ATF6.
Teodoro, Tracy. "Examining the Role of Endoplasmic Reticulum Stress in Pancreatic Beta-cell Biology". Thesis, 2012. http://hdl.handle.net/1807/32825.
Texto completoAmyot, Julie. "Rôles du stress du réticulum endoplasmique et de l'immunité innée dans l'inhibition de la transcription du gène de l'insuline : étude du facteur de transcription ATF6 et du récepteur TLR4". Thèse, 2011. http://hdl.handle.net/1866/6961.
Texto completoType 2 diabetes is characterized by insulin resistance and impaired insulin secretion from the pancreatic β-cell. Endoplasmic reticulum (ER) stress and innate immunity have both been reported to alter pancreatic β-cell function. However, it is not clear whether these factors can affect the transcription of the insulin gene. The aim of this thesis was to assess the role of ER stress and innate immunity in the regulation of the insulin gene. Pancreatic β-cells have a well-developed endoplasmic reticulum (ER) due to their highly specialized secretory function to produce insulin in response to glucose and nutrients. In a first study, using several approaches we showed that ATF6 (activating transcription factor 6), a protein implicated in the ER stress response, directly binds to the A5/Core of the insulin gene promoter in isolated rat islets. We also showed that overexpression of the active (cleaved) fragment of ATF6α, but not ATF6β, inhibits the activity of an insulin promoter-reporter construct. However, the inhibitory effect of ATF6α was insensitive to mutational inactivation or deletion of the A5/Core. Therefore, although ATF6 binds directly to the A5/Core of the rat insulin II gene promoter, this direct binding does not appear to contribute to its repressive activity. In recent years, the gut microbiota was proposed has an environmental factor increasing the risk of type 2 diabetes. Subjects with diabetes have higher circulating levels of lipopolysaccharides (LPS) than non-diabetic patients. Recent observations suggest that the signalling cascade activated by LPS binding to Toll-Like Receptor 4 (TLR4) exerts deleterious effects on pancreatic β-cell function; however, the molecular mechanisms of these effects are incompletely understood. We showed that exposure of isolated human, rat and mouse islets of Langerhans to LPS dose-dependently reduced insulin gene expression. This was associated in mouse and rat islets with decreased mRNA expression of two key transcription factors of the insulin gene, PDX-1 (pancreatic duodenal homeobox 1) and MafA (mammalian homologue of avian MafA/L-Maf). LPS repression of insulin, PDX-1 and MafA expression was not observed in islets from TLR4-deficient mice and was completely prevented in rat islets by inhibition of the NF-kB signalling pathway. These results demonstrate that LPS inhibits β-cell gene expression in a TLR4-dependent manner and via NF-kB signaling in pancreatic islets, suggesting a novel mechanism by which the gut microbiota might affect pancreatic β-cell function. Our findings provide a better understanding of the molecular mechanisms underlying insulin gene repression in type 2 diabetes, and suggest potential therapeutic targets that might prevent or delay the decline of β-cell function in the course of type 2 diabetes, which affects more than two million Canadians.