title: Cdk1-mediated phosphorylation of human ATF7 at Thr-51 and Thr-53 promotes cell-cycle progression into M phase.
abstract: Activating transcription factor 2 (ATF2) and its homolog ATF7 are phosphorylated at Thr-69/Thr-71 and at Thr-51/Thr-53, respectively, by stress-activated MAPKs regulating their transcriptional functions in G1 and S phases. However, little is known about the role of ATF2 and ATF7 in G2/M phase. Here, we show that Cdk1-cyclin B1 phosphorylates ATF2 at Thr-69/Thr-71 and ATF7 at Thr-51/Thr-53 from early prophase to anaphase in the absence of any stress stimulation. Knockdown of ATF2 or ATF7 decreases the rate of cell proliferation and the number of cells in M-phase. In particular, the knockdown of ATF7 severely inhibits cell proliferation and G2/M progression. The inducible expression of a mitotically nonphosphorylatable version of ATF7 inhibits G2/M progression despite the presence of endogenous ATF7. We also show that mitotic phosphorylation of ATF7 promotes the activation of Aurora kinases, which are key enzymes for early mitotic events. These results suggest that the Cdk1-mediated phosphorylation of ATF7 facilitates G2/M progression, at least in part, by enabling Aurora signaling.
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kubota
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yamaguchi
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Ryuzaburo
authors.initials: R
authors.lastname: Yuki
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Nakajo
authors.affiliation: Department of Biochemistry and Molecular Biology, Rutgers New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Eckner
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Yamaguchi
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Kazunari K
authors.initials: KK
authors.lastname: Yokoyama
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamaguchi
mesh_terms: D051698:Activating Transcription Factor 2 / Q000737:chemistry / Q000378:metabolism; D051696:Activating Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000705:Anaphase; D064127:Aurora Kinases / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002455:Cell Division; D016195:G2 Phase; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism*; D011418:Prophase
chemical_list: C497105:ATF2 protein, human; C427752:ATF7 protein, human; D051698:Activating Transcription Factor 2; D051696:Activating Transcription Factors; D010769:Phosphothreonine; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase