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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Raychaudhuri, Pradip Dominguez-brauer, Carmen Chen, Yi-ju Asara, John M. Lau, Lester F. Wang, Zebin Tyner, Angela L. Costa, Robert H. |
| Description | Author Affiliation: Chen YJ ( Department of Biochemistry and Molecular Genetics, University of Illinois, College of Medicine, Chicago, Illinois 60607, USA.) |
| Abstract | The Forkhead box M1 (FoxM1) transcription factor is critical for expression of the genes essential for G(1)/S transition and mitotic progression. To explore the cell cycle regulation of FoxM1, we examined the phosphorylation profile of FoxM1. Here, we show that the phosphorylated status and the activity of FoxM1 increase as cells progress from S to G(2)/M phases. Moreover, dephosphorylation of FoxM1 coincides with exit from mitosis. Using mass spectrometry, we have identified a new conserved phosphorylation site (Ser-251) within the forkhead domain of FoxM1. Disruption of Ser-251 inhibits phosphorylation of FoxM1 and dramatically decreases its transcriptional activity. We demonstrate that the Ser-251 residue is required for CDK1-dependent phosphorylation of FoxM1 as well as its interaction with the coactivator CREB-binding protein (CBP). Interestingly, the transcriptional activity of the S251A mutant protein remains responsive to activation by overexpressed Polo-like kinase 1 (PLK1). Cells expressing the S251A mutant exhibit reduced expression of the G(2)/M phase genes and impaired mitotic progression. Our results demonstrate that the transcriptional activity of FoxM1 is controlled in a cell cycle-dependent fashion by temporally regulated phosphorylation and dephosphorylation events, and that the phosphorylation at Ser-251 is critical for the activation of FoxM1. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 44 |
| Volume Number | 284 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2009-10-30 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CDC2 Protein Kinase Metabolism Forkhead Transcription Factors Binding Sites CREB-Binding Protein Cell Cycle Cell Line, Tumor Conserved Sequence Phosphorylation Serine Transcription, Genetic Research Support, N.I.H., Extramural Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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