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

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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 Wnt/β-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 β-catenin in preventing the histone deacetylase 1-dependent inhibitory functions of several DNA-binding transcriptional repressors, potentially including E2F4/p130 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, β-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.

Original languageEnglish (US)
Pages (from-to)3245-3250
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number6
DOIs
StatePublished - Mar 18 2003

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Baek, S. H., Kioussi, C., Briata, P., Wang, D., Nguyen, H. D., Ohgi, K. A., Glass, C. K., Wynshaw-Boris, A., Rose, D. W., & Rosenfeld, M. G. (2003). Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway. Proceedings of the National Academy of Sciences of the United States of America, 100(6), 3245-3250. https://doi.org/10.1073/pnas.0330217100