Phosphorylation of CPAP by Aurora-A Maintains Spindle Pole Integrity during Mitosis

Article English OPEN
En-Ju Chou ; Liang-Yi Hung ; Chieh-Ju C. Tang ; Wen-Bin Hsu ; Hsin-Yi Wu ; Pao-Chi Liao ; Tang K. Tang (2016)
  • Publisher: Elsevier
  • Journal: Cell Reports, volume 14, issue 12, pages 2,975-2,987 (issn: 2211-1247)
  • Related identifiers: doi: 10.1016/j.celrep.2016.02.085
  • Subject: Biology (General) | QH301-705.5
    mesheuropmc: nervous system diseases | therapeutics | respiratory tract diseases | enzymes and coenzymes (carbohydrates) | circulatory and respiratory physiology

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.
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