Regulation of FOXO1-mediated transcription and cell proliferation by PARP-1.
Forkhead box O (FOXO) transcription factors play an important role in a wide range of biological processes, including cell cycle control, apoptosis, detoxification of reactive oxygen species, and gluconeogenesis through regulation of gene expression. In this study, we demonstrated that PARP-1 functions as a negative regulator of FOXO1. We showed ... that PARP-1 directly binds to and poly(ADP-ribosyl)ates FOXO1 protein. PARP-1 represses FOXO1-mediated expression of cell cycle inhibitor p27(Kip1) gene. Notably, poly(ADP-ribosyl)ation activity was not required for the repressive effect of PARP-1 on FOXO1 function. Furthermore, knockdown of PARP-1 led to a decrease in cell proliferation in a manner dependent on FOXO1 function. Chromatin immunoprecipitation experiments confirmed that PARP-1 is recruited to the p27(Kip1) gene promoter through a binding to FOXO1. These results suggest that PARP-1 acts as a corepressor for FOXO1, which could play an important role in proper cell proliferation by regulating p27(Kip1) gene expression.
Mesh Terms:
Cell Line, Cell Proliferation, Forkhead Transcription Factors, Gene Expression Regulation, Humans, Intracellular Signaling Peptides and Proteins, Phosphorylation, Poly Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Promoter Regions, Genetic, Proteins, Proto-Oncogene Proteins c-akt, Repressor Proteins, Transcription, Genetic
Cell Line, Cell Proliferation, Forkhead Transcription Factors, Gene Expression Regulation, Humans, Intracellular Signaling Peptides and Proteins, Phosphorylation, Poly Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Promoter Regions, Genetic, Proteins, Proto-Oncogene Proteins c-akt, Repressor Proteins, Transcription, Genetic
Biochem. Biophys. Res. Commun.
Date: May. 08, 2009
PubMed ID: 19281796
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