1. Cell Cycle-dependent Regulation of the Forkhead Transcription Factor FOXK2 by CDK·Cyclin Complexes
- Author
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Eberhard Krause, Anett Marais, Zongling Ji, Andrew D. Sharrocks, Emma S. Child, and David J. Mann
- Subjects
Cyclin A ,Apoptosis ,Polo-like kinase ,Biochemistry ,Mass Spectrometry ,Protein Phosphorylation ,0302 clinical medicine ,Serine ,Phosphorylation ,0303 health sciences ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Cycle ,CDK (Cyclin-dependent Kinase) ,Forkhead Transcription Factors ,Cell cycle ,Cyclin-Dependent Kinases ,Cell biology ,FoxK2 ,030220 oncology & carcinogenesis ,RNA Interference ,Restriction point ,CDC2 Protein Kinase ,Protein Binding ,Green Fluorescent Proteins ,Immunoblotting ,Molecular Sequence Data ,Transfection ,03 medical and health sciences ,Cyclin-dependent kinase ,Cell Line, Tumor ,Cyclins ,Humans ,Immunoprecipitation ,Gene Regulation ,Amino Acid Sequence ,Cyclin B1 ,Molecular Biology ,030304 developmental biology ,Cyclin-dependent kinase 2 ,Cell Biology ,Molecular biology ,Forkhead ,Gene Transcription ,Transcription Factors ,HEK293 Cells ,Microscopy, Fluorescence ,Mutation ,biology.protein ,HeLa Cells - Abstract
Several mammalian forkhead transcription factors have been shown to impact on cell cycle regulation and are themselves linked to cell cycle control systems. Here we have investigated the little studied mammalian forkhead transcription factor FOXK2 and demonstrate that it is subject to control by cell cycle-regulated protein kinases. FOXK2 exhibits a periodic rise in its phosphorylation levels during the cell cycle, with hyperphosphorylation occurring in mitotic cells. Hyperphosphorylation occurs in a cyclin-dependent kinase (CDK)·cyclin-dependent manner with CDK1·cyclin B as the major kinase complex, although CDK2 and cyclin A also appear to be important. We have mapped two CDK phosphorylation sites, serines 368 and 423, which play a role in defining FOXK2 function through regulating its stability and its activity as a transcriptional repressor protein. These two CDK sites appear vital for FOXK2 function because expression of a mutant lacking these sites cannot be tolerated and causes apoptosis.
- Published
- 2010
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