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 mitosis5. Here we report that Forkhead Box M1 (FoxM1), a substrate of Plk1, 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.
authors.affiliation: Department of Urology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.forename: Liviu
authors.initials: L
authors.lastname: Malureanu
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Deursen
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Tindall
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism*; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016195:G2 Phase; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C107585:FOXM1 protein, human