title: Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway.
abstract: Pitx2 is a bicoid-related homeodomain factor that is required for effective cell type-specific proliferation directly activating a specific growth-regulating gene cyclin D2. Here, we report that Pitx2, in response to the Wntbeta-catenin pathway and growth signals, also can regulate c-Myc and cyclin D1. Investigation of molecular mechanisms required for Pitx2-dependent proliferation, in these cases, further supports a nuclear role for beta-catenin in preventing the histone deacetylase 1-dependent inhibitory functions of several DNA-binding transcriptional repressors, potentially including E2F4p130 pocket protein inhibitory complex, as well as lymphoid enhancer factor 1 and Pitx2, by dismissal of histone deacetylase 1 and loss of its enzymatic activity. Thus, beta-catenin plays a signal-integrating role in Wnt- and growth factor-dependent proliferation events in mammalian development by both derepressing several classes of repressors and by activating Pitx2, regulating the activity of several growth control genes.
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Baek
authors.forename: Chrissa
authors.initials: C
authors.lastname: Kioussi
authors.forename: Paola
authors.initials: P
authors.lastname: Briata
authors.forename: Degeng
authors.initials: D
authors.lastname: Wang
authors.forename: H D
authors.initials: HD
authors.lastname: Nguyen
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Ohgi
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Glass
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
authors.forename: David W
authors.initials: DW
authors.lastname: Rose
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D056742:Cyclin D2; D016213:Cyclins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016193:G1 Phase / Q000235:genetics* / Q000502:physiology; D016259:Genes, myc; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D000097577:Homeobox Protein PITX2
chemical_list: D019938:Cyclin D1; D056742:Cyclin D2; D016213:Cyclins; D003598:Cytoskeletal Proteins; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D000097577:Homeobox Protein PITX2; C080336:CCND2 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C486196:Ccnd2 protein, mouse; C539127:NCOR1 protein, human; C539128:Ncor1 protein, mouse; C110550:HDAC1 protein, human