Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 28, Issue 25, Pages 3699-3708Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E17-01-0076
Keywords
-
Categories
Funding
- Azm AMP
- Saade Association
- Agence Nationale de la Recherche Grant [ANR-11-LABX-0015]
- Grants-in-Aid for Scientific Research [16H05140] Funding Source: KAKEN
Ask authors/readers for more resources
The beta(4) isoform of the beta-subunits of voltage-gated calcium channel regulates cell proliferation and cell cycle progression. Herein we show that coexpression of the beta(4)-subunit with actors of the canonical Wnt/beta-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. beta(4)-subunit-mediated inhibition of Wnt signaling is observed in the presence of LiCl, an inhibitor of glycogen synthase kinase (GSK3) that promotes beta-catenin translocation to the nucleus. Expression of beta(4)-subunit mutants that lost the ability to translocate to the nucleus has no effect on Wnt signaling, suggesting that beta(4)-subunit inhibition of Wnt signaling occurs downstream from GSK3 and requires targeting of beta(4)-subunit to the nucleus. beta(4)-subunit coimmunoprecipitates with the TCF4 transcription factor and overexpression of TCF4 reverses the effect of beta(4)-subunit on the Wnt pathway. We thus propose that the interaction of nuclear beta(4)-subunit with TCF4 prevents beta-catenin binding to TCF4 and leads to the inhibition of the Wnt-responsive gene transcription. Thereby, our results show that beta(4)-subunit is a TCF4 repressor and therefore appears as an interesting candidate for the regulation of this pathway in neurons where beta(4)-subunit is specifically expressed.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available