Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression

Zheng Fu; Liviu Malureanu; Jun Huang; Wei Wang; Hao Li; Jan M. van Deursen; Donald J. Tindall; Junjie Chen

doi:10.1038/ncb1767

Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression

Zheng Fu, Liviu Malureanu, Jun Huang, Wei Wang, Hao Li, Jan M. van Deursen, Donald J. Tindall, Junjie Chen

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214 Scopus citations

Abstract

Proper control of entry into and progression through mitosis is essential for normal cell proliferation and the maintenance of genome stability. The mammalian mitotic kinase Polo-like kinase 1 (Plk1) is involved in multiple stages of mitosis. Here we report that Forkhead Box M1 (FoxM1), a substrate of Plk1 (refs 6, 7, 8), controls a transcriptional programme that mediates Plk1-dependent regulation of cell-cycle progression. The carboxy-terminal domain of FoxM1 binds Plk1, and phosphorylation of two key residues in this domain by Cdk1 is essential for Plk1-FoxM1 interaction. Formation of the Plk1-FoxM1 complex allows for direct phosphorylation of FoxM1 by Plk1 at G2/M and the subsequent activation of FoxM1 activity, which is required for expression of key mitotic regulators, including Plk1 itself. Thus, Plk1-dependent regulation of FoxM1 activity provides a positive-feedback loop ensuring tight regulation of transcriptional networks essential for orderly mitotic progression.

Original language	English (US)
Pages (from-to)	1076-1082
Number of pages	7
Journal	Nature Cell Biology
Volume	10
Issue number	9
DOIs	https://doi.org/10.1038/ncb1767
State	Published - 2008

ASJC Scopus subject areas

Cell Biology

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title = "Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression",

abstract = "Proper control of entry into and progression through mitosis is essential for normal cell proliferation and the maintenance of genome stability. The mammalian mitotic kinase Polo-like kinase 1 (Plk1) is involved in multiple stages of mitosis. Here we report that Forkhead Box M1 (FoxM1), a substrate of Plk1 (refs 6, 7, 8), controls a transcriptional programme that mediates Plk1-dependent regulation of cell-cycle progression. The carboxy-terminal domain of FoxM1 binds Plk1, and phosphorylation of two key residues in this domain by Cdk1 is essential for Plk1-FoxM1 interaction. Formation of the Plk1-FoxM1 complex allows for direct phosphorylation of FoxM1 by Plk1 at G2/M and the subsequent activation of FoxM1 activity, which is required for expression of key mitotic regulators, including Plk1 itself. Thus, Plk1-dependent regulation of FoxM1 activity provides a positive-feedback loop ensuring tight regulation of transcriptional networks essential for orderly mitotic progression.",

author = "Zheng Fu and Liviu Malureanu and Jun Huang and Wei Wang and Hao Li and {van Deursen}, {Jan M.} and Tindall, {Donald J.} and Junjie Chen",

note = "Funding Information: We are grateful for extensive discussions with R.H. Medema and J. Laoukili and their input. We thank H.M. Thompson for editing the manuscript. Mass spectrometry analysis was performed by Taplin Biological Mass Spectrometry Facility at Harvard University. This work was supported in part by grants from the National Institutes of Health (NIH RO1 CA113381 to JC), Mayo SPORE P50 (CA116201 project no. 1 to J.C.) and the T.J. Martell Foundation (to D.J.T.). J.C. is a recipient of an Era of Hope Scholars award from DOD. Z.F. is a recipient of a Ruth L. Kirschstein NRSA individual Fellowship from NIH.",

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AU - Li, Hao

AU - van Deursen, Jan M.

AU - Tindall, Donald J.

AU - Chen, Junjie

N1 - Funding Information: We are grateful for extensive discussions with R.H. Medema and J. Laoukili and their input. We thank H.M. Thompson for editing the manuscript. Mass spectrometry analysis was performed by Taplin Biological Mass Spectrometry Facility at Harvard University. This work was supported in part by grants from the National Institutes of Health (NIH RO1 CA113381 to JC), Mayo SPORE P50 (CA116201 project no. 1 to J.C.) and the T.J. Martell Foundation (to D.J.T.). J.C. is a recipient of an Era of Hope Scholars award from DOD. Z.F. is a recipient of a Ruth L. Kirschstein NRSA individual Fellowship from NIH.

PY - 2008

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N2 - Proper control of entry into and progression through mitosis is essential for normal cell proliferation and the maintenance of genome stability. The mammalian mitotic kinase Polo-like kinase 1 (Plk1) is involved in multiple stages of mitosis. Here we report that Forkhead Box M1 (FoxM1), a substrate of Plk1 (refs 6, 7, 8), controls a transcriptional programme that mediates Plk1-dependent regulation of cell-cycle progression. The carboxy-terminal domain of FoxM1 binds Plk1, and phosphorylation of two key residues in this domain by Cdk1 is essential for Plk1-FoxM1 interaction. Formation of the Plk1-FoxM1 complex allows for direct phosphorylation of FoxM1 by Plk1 at G2/M and the subsequent activation of FoxM1 activity, which is required for expression of key mitotic regulators, including Plk1 itself. Thus, Plk1-dependent regulation of FoxM1 activity provides a positive-feedback loop ensuring tight regulation of transcriptional networks essential for orderly mitotic progression.

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Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression

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