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

Proper control of entry into and progression through mitosis is essential for normal cell proliferation and the maintenance of genome stability(1-4). The mammalian mitotic kinase Polo-like kinase 1 (Plk1) is involved in multiple stages of mitosis(5). Here we report that Forkhead Box M1 (FoxM1), a substrate of Plk1 (refs 6-8), 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.