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Cell Rep. 2016 Mar 29;14(12):2975-87. doi: 10.1016/j.celrep.2016.02.085. Epub 2016 Mar 17.

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

Author information

1
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
2
Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan 70101, Taiwan.
3
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
4
Department of Environmental and Occupational Health, National Cheng Kung University, Tainan 70101, Taiwan.
5
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan. Electronic address: tktang@ibms.sinica.edu.tw.

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.

PMID:
26997271
DOI:
10.1016/j.celrep.2016.02.085
[Indexed for MEDLINE]
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