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

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Abstract
The kinase Plk1 regulates multiple processes during mitosis in mammalian cells. Chen and colleagues show that Plk1 also controls a transcriptional network required for orderly cell-cycle progression through Cdk1-dependent phosphorylation of the transcription factor FoxM1 Proper control of entry into and progression through mitosis is essential for normal cell proliferation and the maintenance of genome stability1,2,3,4. The mammalian mitotic kinase Polo-like kinase 1 (Plk1) is involved in multiple stages of mitosis5. 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.