title: Novel interactions between FOXM1 and CDC25A regulate the cell cycle.
abstract: FOXM1 is a critical regulator of the G1/S and G2/M cell cycle transitions, as well as of the mitotic spindle assembly. Previous studies have suggested that FOXM1 regulates CDC25A gene transcription, but the mechanism remains unknown. Here, we provide evidence that FOXM1 directly regulates CDC25A gene transcription via direct promoter binding and indirect activation of E2F-dependent pathways. Prior literature reported that CDC25B and CDC25C activate CDK1/cyclinB complexes in order to enable phosphorylation of FOXM1. It was unknown if CDC25A functions in a similar manner. We report that FOXM1 transcriptional activity is synergistically enhanced when co-expressed with CDC25A. The increase is dependent upon CDK1 phosphorylation of FOXM1 at T600, T611 and T620 residues. We also report a novel protein interaction between FOXM1 and CDC25A via the C-terminus of FOXM1. We demonstrate that the phosphorylation of Thr 600 and Thr 611 residues of FOXM1 enhanced this interaction, and that the interaction is dependent upon CDC25A phosphatase activity. Our work provides novel insight into the underlying mechanisms by which FOXM1 controls the cell cycle through its association with CDC25A.
authors.affiliation: Maine Institute for Human Genetics and Health, Brewer, Maine, United States of America.
authors.forename: Con
authors.initials: C
authors.lastname: Sullivan
authors.forename: Youhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Shen
authors.forename: Adam
authors.initials: A
authors.lastname: Curtis
authors.forename: Christina
authors.initials: C
authors.lastname: Newman
authors.forename: Janet M
authors.initials: JM
authors.lastname: Hock
authors.forename: Xiong
authors.initials: X
authors.lastname: Li
mesh_terms: D059447:Cell Cycle Checkpoints / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases