title: p120-catenin regulates REST and CoREST, and modulates mouse embryonic stem cell differentiation.
abstract: 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.
authors: Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Program in Genes and Development, The University of Texas Graduate School of Biomedical Science-Houston, Houston, TX 77030, USA.
authors: Moonsup
authors: M
authors: Lee
authors: Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Hong
authors: H
authors: Ji
authors: Laboratory for Animal Resources and Genetic Engineering, Riken Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors: Yasuhide
authors: Y
authors: Furuta
authors: Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
authors: Jae-il
authors: JI
authors: Park
authors: Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Program in Genes and Development, The University of Texas Graduate School of Biomedical Science-Houston, Houston, TX 77030, USA pdmccrea@mdanderson.org.
authors: Pierre D
authors: PD
authors: McCrea
mesh_terms: D000818:Animals; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D056970:Co-Repressor Proteins; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D000095002:Delta Catenin; D000099229:RE1-Silencing Transcription Factor
chemical_list: D051177:Catenins; D056970:Co-Repressor Proteins; D009419:Nerve Tissue Proteins; D050814:Octamer Transcription Factor-3; D012097:Repressor Proteins; D000095002:Delta Catenin; D000099229:RE1-Silencing Transcription Factor; C494174:Pou5f1 protein, mouse; C485650:Rcor2 protein, mouse
keywords: CoREST; E-cadherin; Mouse embryonic stem cell; REST; p120-catenin