Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway.
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.
Baek
Sung Hee
SH
Howard Hughes Medical Institute, Department of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA.
Kioussi
Chrissa
C
Briata
Paola
P
Wang
Degeng
D
Nguyen
H D
HD
Ohgi
Kenneth A
KA
Glass
Christopher K
CK
Wynshaw-Boris
Anthony
A
Rose
David W
DW
Rosenfeld
Michael G
MG
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
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