XB-ART-49317
J Cell Sci
2014 Sep 15;127Pt 18:4037-51. doi: 10.1242/jcs.151944.
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p120-catenin regulates REST and CoREST, and modulates mouse embryonic stem cell differentiation.
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Although the canonical Wnt pathway and β-catenin have been extensively studied, less is known about the role of p120-catenin (also known as δ1-catenin) in the nuclear compartment. Here, we report that p120-catenin binds and negatively regulates REST and CoREST (also known as Rcor1), a repressive transcriptional complex that has diverse developmental and pathological roles. Using mouse embryonic stem cells (mESCs), mammalian cell lines, Xenopus embryos and in vitro systems, we find that p120-catenin directly binds the REST-CoREST complex, displacing it from established gene targets to permit their transcriptional activation. Importantly, p120-catenin levels further modulate the mRNA and protein levels of Oct4 (also known as POU5F1), Nanog and Sox2, and have an impact upon the differentiation of mESCs towards neural fates. In assessing potential upstream inputs to this new p120-catenin-REST-CoREST pathway, REST gene targets were found to respond to the level of E-cadherin, with evidence suggesting that p120-catenin transduces signals between E-cadherin and the nucleus. In summary, we provide the first evidence for a direct upstream modulator and/or pathway regulating REST-CoREST, and reveal a substantial role for p120-catenin in the modulation of stem cell differentiation.
???displayArticle.pubmedLink??? 25074806
???displayArticle.pmcLink??? PMC4163646
???displayArticle.link??? J Cell Sci
???displayArticle.grants??? [+]
CA-16672 NCI NIH HHS , R01 GM52112 NIGMS NIH HHS , P30 CA016672 NCI NIH HHS , R01 GM107079 NIGMS NIH HHS , R01 GM052112 NIGMS NIH HHS
Species referenced: Xenopus laevis
Genes referenced: ctnnd1 pou5f3 rcor1 sox2
???displayArticle.morpholinos??? ctnnd1 MO1 ctnnd1 MO2
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