Down-regulation of the Wnt/β-catenin signaling pathway by Cacnb4
| العنوان: | Down-regulation of the Wnt/β-catenin signaling pathway by Cacnb4 |
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| المؤلفون: | Juan L. Brusés, Yasuo Mori, Michel Ronjat, Lydie Lefrançois, Michel De Waard, Mohamad Rima, Anaïs Lopez, Philippe Merle, Marwa Daghsni, Mireia Duñach, Ziad Fajloun |
| المساهمون: | Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biochimie - Ingénierie des protéines, Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Departament de Bioquímica i Biotecnologia - Department of Biochemistry and Biotechnology [Tarragone], Universitat Rovira i Virgili, Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Mercy College, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Kyoto University [Kyoto] |
| المصدر: | Recercat. Dipósit de la Recerca de Catalunya instname Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) Molecular Biology of the Cell Molecular Biology of the Cell, 2017, Equipe IIb, 28 (25), pp.3699--3708. ⟨10.1091/mbc.E17-01-0076⟩ Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Molecular Biology of the Cell, American Society for Cell Biology, 2017, Equipe IIb, 28 (25), pp.3699--3708. ⟨10.1091/mbc.E17-01-0076⟩ |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Frizzled, [SDV]Life Sciences [q-bio], Down-Regulation, CHO Cells, Biology, Suppressor of cytokine signalling, Cell Line, 03 medical and health sciences, Glycogen Synthase Kinase 3, 0302 clinical medicine, Cricetulus, Transcription Factor 4, Cell Line, Tumor, Animals, Humans, Autocrine signalling, Promoter Regions, Genetic, Molecular Biology, Wnt Signaling Pathway, beta Catenin, Cell Proliferation, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Wnt signaling pathway, LRP6, LRP5, Cell Biology, Articles, Signaling, Cell biology, Wnt Proteins, 030104 developmental biology, Hes3 signaling axis, Calcium Channels, Signal transduction, 030217 neurology & neurosurgery, Protein Binding, Signal Transduction, Transcription Factors |
| الوصف: | The cytoplasmic β4-subunit of the voltage-gated calcium channels has been shown be involved in the regulation of gene transcription. This subunit interacts with the transcription factor TCF4 and inhibits the Wnt/β-catenin signaling pathway. These results may also explain the inhibitory effect of the β4-subunit on cell proliferation. The β4 isoform of the β-subunits of voltage-gated calcium channel regulates cell proliferation and cell cycle progression. Herein we show that coexpression of the β4-subunit with actors of the canonical Wnt/β-catenin signaling pathway in a hepatoma cell line inhibits Wnt-responsive gene transcription and decreases cell division, in agreement with the role of the Wnt pathway in cell proliferation. β4-subunit–mediated inhibition of Wnt signaling is observed in the presence of LiCl, an inhibitor of glycogen synthase kinase (GSK3) that promotes β-catenin translocation to the nucleus. Expression of β4-subunit mutants that lost the ability to translocate to the nucleus has no effect on Wnt signaling, suggesting that β4-subunit inhibition of Wnt signaling occurs downstream from GSK3 and requires targeting of β4-subunit to the nucleus. β4-subunit coimmunoprecipitates with the TCF4 transcription factor and overexpression of TCF4 reverses the effect of β4-subunit on the Wnt pathway. We thus propose that the interaction of nuclear β4-subunit with TCF4 prevents β-catenin binding to TCF4 and leads to the inhibition of the Wnt-responsive gene transcription. Thereby, our results show that β4-subunit is a TCF4 repressor and therefore appears as an interesting candidate for the regulation of this pathway in neurons where β4-subunit is specifically expressed. |
| وصف الملف: | application/pdf |
| تدمد: | 1939-4586 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::76231d0bbcbb922bc276adff93e77c6f http://hdl.handle.net/2072/428227 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....76231d0bbcbb922bc276adff93e77c6f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19394586 |
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