Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway

Sung Hee Baek; Chrissa Kioussi; Paola Briata; Degeng Wang; H D Nguyen; Kenneth A Ohgi; Christopher K Glass; Anthony Wynshaw-Boris; David W Rose; Michael G Rosenfeld

doi:10.1073/pnas.0330217100

Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway

Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3245-50. doi: 10.1073/pnas.0330217100. Epub 2003 Mar 10.

Authors

Sung Hee Baek¹, Chrissa Kioussi, Paola Briata, Degeng Wang, H D Nguyen, Kenneth A Ohgi, Christopher K Glass, Anthony Wynshaw-Boris, David W Rose, Michael G Rosenfeld

Affiliation

¹ Howard Hughes Medical Institute, Department of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Cell Line
Colonic Neoplasms / genetics
Colonic Neoplasms / metabolism
Cyclin D1 / metabolism
Cyclin D2
Cyclins / metabolism
Cytoskeletal Proteins / metabolism
G1 Phase / genetics*
G1 Phase / physiology
Genes, myc
Histone Deacetylase 1
Histone Deacetylases / metabolism
Homeobox Protein PITX2
Homeodomain Proteins / metabolism*
Humans
Mice
Mice, Knockout
Nuclear Proteins / metabolism
Nuclear Receptor Co-Repressor 1
Promoter Regions, Genetic
Proto-Oncogene Proteins / metabolism*
Repressor Proteins / metabolism
Signal Transduction
Trans-Activators / metabolism
Transcription Factors / metabolism*
Tumor Cells, Cultured
Wnt Proteins
Zebrafish Proteins*
beta Catenin

Substances

CCND2 protein, human
CTNNB1 protein, human
CTNNB1 protein, mouse
Ccnd2 protein, mouse
Cyclin D2
Cyclins
Cytoskeletal Proteins
Homeodomain Proteins
NCOR1 protein, human
Ncor1 protein, mouse
Nuclear Proteins
Nuclear Receptor Co-Repressor 1
Proto-Oncogene Proteins
Repressor Proteins
Trans-Activators
Transcription Factors
Wnt Proteins
Zebrafish Proteins
beta Catenin
Cyclin D1
HDAC1 protein, human
Histone Deacetylase 1
Histone Deacetylases

Grants and funding

R01 NS073159/NS/NINDS NIH HHS/United States