title: Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis.
abstract: Centrosomes in mammalian cells have recently been implicated in cytokinesis; however, their role in this process is poorly defined. Here, we describe a human coiled-coil protein, Cep55 (centrosome protein 55 kDa), that localizes to the mother centriole during interphase. Despite its association with gamma-TuRC anchoring proteins CG-NAP and Kendrin, Cep55 is not required for microtubule nucleation. Upon mitotic entry, centrosome dissociation of Cep55 is triggered by Erk2/Cdk1-dependent phosphorylation at S425 and S428. Furthermore, Cep55 locates to the midbody and plays a role in cytokinesis, as its depletion by siRNA results in failure of this process. S425/428 phosphorylation is required for interaction with Plk1, enabling phosphorylation of Cep55 at S436. Cells expressing phosphorylation-deficient mutant forms of Cep55 undergo cytokinesis failure. These results highlight the centrosome as a site to organize phosphorylation of Cep55, enabling it to relocate to the midbody to function in mitotic exit and cytokinesis.
authors.affiliation: Queensland Institute of Medical Research, P.O. Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia.
authors.forename: Megan
authors.initials: M
authors.lastname: Fabbro
authors.forename: Bin-Bing
authors.initials: BB
authors.lastname: Zhou
authors.forename: Mikiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Boris
authors.initials: B
authors.lastname: Sarcevic
authors.forename: Preeti
authors.initials: P
authors.lastname: Lal
authors.forename: Mark E
authors.initials: ME
authors.lastname: Graham
authors.forename: Brian G
authors.initials: BG
authors.lastname: Gabrielli
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Robinson
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ono
authors.forename: Kum Kum
authors.initials: KK
authors.lastname: Khanna
mesh_terms: D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D019295:Computational Biology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014018:Tissue Distribution; D000097869:Polo-Like Kinase 1
chemical_list: D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D016203:CDC2 Protein Kinase; D002148:Calmodulin-Binding Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D019950:Mitogen-Activated Protein Kinase 1; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1; C119719:AKAP9 protein, human; C505378:Cep55 protein, human; C410004:kendrin