Down-regulation of the Wnt/β-catenin signaling pathway by Cacnb4

Autor: Juan L. Brusés, Yasuo Mori, Michel Ronjat, Lydie Lefrançois, Michel De Waard, Mohamad Rima, Anaïs Lopez, Philippe Merle, Marwa Daghsni, Mireia Duñach, Ziad Fajloun
Přispěvatelé: 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]
Rok vydání: 2021
Předmět:
Zdroj: 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⟩
ISSN: 1939-4586
DOI: 10.1091/mbc.E17-01-0076⟩
Popis: 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.
Databáze: OpenAIRE
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