title: Phosphorylation of CPAP by Aurora-A Maintains Spindle Pole Integrity during Mitosis.
abstract: CPAP is required for centriole elongation during S/G2 phase, but the role of CPAP in mitosis is incompletely understood. Here, we show that CPAP maintains spindle pole integrity through its phosphorylation by Aurora-A during mitosis. Depletion of CPAP induced a prolonged delay in mitosis, pericentriolar material (PCM) dispersion, and multiple mitotic abnormalities. Further studies demonstrated that CPAP directly interacts with and is phosphorylated by Aurora-A at serine 467 during mitosis. Interestingly, the dispersal of the PCM was effectively rescued by ectopic expression of wild-type CPAP or a phospho-mimic CPAP-S467D mutant, but not a non-phosphorylated CPAP-S467A mutant. Finally, we found that CPAP-S467D has a low affinity for microtubule binding but a high affinity for PCM proteins. Together, our results support a model wherein CPAP is required for proper mitotic progression, and phosphorylation of CPAP by Aurora-A is essential for maintaining spindle pole integrity.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: En-Ju
authors.initials: EJ
authors.lastname: Chou
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Liang-Yi
authors.initials: LY
authors.lastname: Hung
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Chieh-Ju C
authors.initials: CJ
authors.lastname: Tang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Hsu
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Wu
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Pao-Chi
authors.initials: PC
authors.lastname: Liao
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan. Electronic address: tktang@ibms.sinica.edu.tw.
authors.forename: Tang K
authors.initials: TK
authors.lastname: Tang
mesh_terms: D000941:Antigens / Q000235:genetics / Q000378:metabolism; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D018385:Centrosome / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D064047:Spindle Poles / Q000502:physiology*; D059008:Time-Lapse Imaging; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D000941:Antigens; C405929:CDK5RAP2 protein, human; C414735:CENPJ protein, human; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D014404:Tubulin; C086178:pericentrin; D064096:Aurora Kinase A