A Conserved Phosphorylation Site within the Forkhead Domain of FoxM1B Is Required for Its Activation by Cyclin-CDK1.

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Title: A Conserved Phosphorylation Site within the Forkhead Domain of FoxM1B Is Required for Its Activation by Cyclin-CDK1.
Authors: Yi-Ju Chen1, Dominguez-Brauer, Carmen1, Zebin Wang1, Asara, John M.2,3, Costat, Robert H.1, Tyner, Angela L.1, Lau, Lester F.1, Raychaudhuri, Pradip1 pradip@uic.edu
Source: Journal of Biological Chemistry. 10/30/2009, Vol. 284 Issue 44, p30695-30707. 13p.
Subjects: Forkhead transcription factors, Cell cycle, Phosphorylation, Cyclins, Protein kinases, Genetic transcription
Abstract: The Forkhead box M1 (FoxM1) transcription factor is critical for expression of the genes essential for G1/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 G2/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-25 1 residue is required for CDK1-dependent phosphorylation of FoxM1 as well as its inter- action 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 G2/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. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: A Conserved Phosphorylation Site within the Forkhead Domain of FoxM1B Is Required for Its Activation by Cyclin-CDK1.
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  Data: <searchLink fieldCode="AR" term="%22Yi-Ju+Chen%22">Yi-Ju Chen</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Dominguez-Brauer%2C+Carmen%22">Dominguez-Brauer, Carmen</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Zebin+Wang%22">Zebin Wang</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Asara%2C+John+M%2E%22">Asara, John M.</searchLink><relatesTo>2,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Costat%2C+Robert+H%2E%22">Costat, Robert H.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Tyner%2C+Angela+L%2E%22">Tyner, Angela L.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Lau%2C+Lester+F%2E%22">Lau, Lester F.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Raychaudhuri%2C+Pradip%22">Raychaudhuri, Pradip</searchLink><relatesTo>1</relatesTo><i> pradip@uic.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 10/30/2009, Vol. 284 Issue 44, p30695-30707. 13p.
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  Data: <searchLink fieldCode="DE" term="%22Forkhead+transcription+factors%22">Forkhead transcription factors</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+cycle%22">Cell cycle</searchLink><br /><searchLink fieldCode="DE" term="%22Phosphorylation%22">Phosphorylation</searchLink><br /><searchLink fieldCode="DE" term="%22Cyclins%22">Cyclins</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+kinases%22">Protein kinases</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+transcription%22">Genetic transcription</searchLink>
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  Data: The Forkhead box M1 (FoxM1) transcription factor is critical for expression of the genes essential for G1/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 G2/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-25 1 residue is required for CDK1-dependent phosphorylation of FoxM1 as well as its inter- action 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 G2/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. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1074/jbc.M109.007997
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        Text: English
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      – SubjectFull: Forkhead transcription factors
        Type: general
      – SubjectFull: Cell cycle
        Type: general
      – SubjectFull: Phosphorylation
        Type: general
      – SubjectFull: Cyclins
        Type: general
      – SubjectFull: Protein kinases
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      – SubjectFull: Genetic transcription
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      – TitleFull: A Conserved Phosphorylation Site within the Forkhead Domain of FoxM1B Is Required for Its Activation by Cyclin-CDK1.
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              Text: 10/30/2009
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              Y: 2009
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