Article ID Journal Published Year Pages File Type
2041408 Cell Reports 2016 13 Pages PDF
Abstract

•Depletion of CPAP induces multiple mitotic abnormalities•CPAP is phosphorylated by Aurora-A at Ser 467 during mitosis•Phosphorylated CPAP coheres PCM proteins and maintains centrosome integrity•Phosphorylated CPAP has a high affinity for PCM proteins but a low affinity for MTs

SummaryCPAP 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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