The β isoform of the β-subunits of voltage-gated calcium channel regulates cell proliferation and cell cycle progression. Herein we show that coexpression of the β-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. β-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 β-subunit mutants that lost the ability to translocate to the nucleus has no effect on Wnt signaling, suggesting that β-subunit inhibition of Wnt signaling occurs downstream from GSK3 and requires targeting of β-subunit to the nucleus. β-subunit coimmunoprecipitates with the TCF4 transcription factor and overexpression of TCF4 reverses the effect of β-subunit on the Wnt pathway. We thus propose that the interaction of nuclear β-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 β-subunit is a TCF4 repressor and therefore appears as an interesting candidate for the regulation of this pathway in neurons where β-subunit is specifically expressed.
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http://dx.doi.org/10.1091/mbc.E17-01-0076 | DOI Listing |
Bone Res
January 2025
Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.
Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor whose dysfunction is linked to developmental dysplasia of the hip, osteoporosis and osteoarthritis. Our work addresses the critical question of how these skeletal pathologies emerge. Here, we show the abundant expression of LRP1 in skeletal progenitor cells at mouse embryonic stage E10.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of Zoology, Aligarh Muslim University, Aligarh 202002, India. Electronic address:
Small molecules are emerging as potential candidates for treating osteoporosis by activating canonical Wnt signaling. These candidates work either by inhibiting DKK-1, sclerostin, SFRP-1, NOTUM, and S1P lyase or by preventing β-catenin degradation through inhibition of GSK-3β, or by targeting Dvl-CXXC5 and axin/β-catenin interactions. While many of these anti-osteoporotic small molecules are in preclinical development, the paucity of FDA-approved small molecules, or promising candidates, that have progressed to clinical trials for treating bone disorders through this mechanism poses a challenge.
View Article and Find Full Text PDFTransl Oncol
January 2025
Department of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China. Electronic address:
Previous studies have demonstrated that intrahepatic cholangiocarcinoma (ICC) may derive from transdifferentiation of hepatocytes, so transforming ICC cells into hepatocytes could be a potential strategy for treating ICC. Hepatocyte nuclear factor 4α (HNF4α), a master transcription factor in the liver, has been demonstrated to induce the differentiation of hepatocellular carcinoma, while its effects on ICC remains unclear. Ivosidenib, an isocitrate dehydrogenase 1 (IDH1) inhibitor, is a novel targeted drug for ICC patients.
View Article and Find Full Text PDFBMC Genomics
January 2025
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Background: Rex rabbit is famous for its silky and soft fur coat, a characteristic predominantly attributed to its hair follicles. Numerous studies have confirmed the crucial roles of mRNAs and non-coding RNAs (ncRNAs) in regulating key cellular processes such as cell proliferation, differentiation, apoptosis and immunity. However, their involvement in the regulation of the hair cycle in Rex rabbits remains unknown.
View Article and Find Full Text PDFGenomics
January 2025
Department of General Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China. Electronic address:
Introduction: Resistance to lenvatinib limits the effectiveness of the targeted treatments for HCC. However, the exact mechanism behind this resistance remains elusive. Current research suggests that circular RNA (circRNA) is pivotal in mediating drug resistance during targeted treatments.
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