Cdk1/Erk2- and Plk1-Dependent Phosphorylation of a Centrosome Protein, Cep55, Is Required for Its Recruitment to Midbody and Cytokinesis

• Published in: Developmental cell 2005-10, Vol.9 (4), p.477-488
• Main Authors: Fabbro, Megan, Zhou, Bin-Bing, Takahashi, Mikiko, Sarcevic, Boris, Lal, Preeti, Graham, Mark E., Gabrielli, Brian G., Robinson, Phillip J., Nigg, Erich A., Ono, Yoshitaka, Khanna, Kum Kum
• Format: Article
• Language: English
• Subjects: A Kinase Anchor Proteins; Adaptor Proteins, Signal Transducing - metabolism; Amino Acid Sequence; Animals; Biological and medical sciences; Calmodulin-Binding Proteins - metabolism; CDC2 Protein Kinase - genetics; CDC2 Protein Kinase - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell differentiation, maturation, development, hematopoiesis; Cell Division - physiology; Cell Line; Cell physiology; Centrosome - metabolism; Centrosome - ultrastructure; Computational Biology; Cytoskeletal Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Molecular and cellular biology; Molecular Sequence Data; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphorylation; Polo-Like Kinase 1; Protein Kinases - genetics; Protein Kinases - metabolism; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Sequence Alignment; Tissue Distribution
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2005.09.003

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 γ-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.