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

En Ju Chou; Liang Yi Hung; Chieh Ju C. Tang; Wen Bin Hsu; Hsin Yi Wu; Pao Chi Liao; Tang K. Tang

doi:10.1016/j.celrep.2016.02.085

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

En Ju Chou, Liang Yi Hung, Chieh Ju C. Tang, Wen Bin Hsu, Hsin Yi Wu, Pao Chi Liao, Tang K. Tang

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25 Citations (Scopus)

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. Chou et al. show that CPAP is essential for proper mitotic progression and maintenance of spindle pole integrity. CPAP is phosphorylated by Aurora-A during mitosis and phosphorylated CPAP coheres PCM proteins and maintains centrosome integrity.

Original language	English
Pages (from-to)	2975-2987
Number of pages	13
Journal	Cell Reports
Volume	14
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2016.02.085
Publication status	Published - 2016 Mar 29

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.celrep.2016.02.085

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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. Chou et al. show that CPAP is essential for proper mitotic progression and maintenance of spindle pole integrity. CPAP is phosphorylated by Aurora-A during mitosis and phosphorylated CPAP coheres PCM proteins and maintains centrosome integrity.",

author = "Chou, {En Ju} and Hung, {Liang Yi} and Tang, {Chieh Ju C.} and Hsu, {Wen Bin} and Wu, {Hsin Yi} and Liao, {Pao Chi} and Tang, {Tang K.}",

note = "Funding Information: We thank Sheau-Hu Chen for technical assistance. This work was supported by an Academia Sinica Investigator Award and by grants from the Thematic Research Program of Academia Sinica (AS-104-TP-B09-1) and the Ministry of Science and Technology (MOST 103-2321-B-001-059 and NSC 103-2321-B001-024). Publisher Copyright: {\textcopyright} 2016 The Authors.",

year = "2016",

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T1 - Phosphorylation of CPAP by Aurora-A Maintains Spindle Pole Integrity during Mitosis

AU - Chou, En Ju

AU - Hung, Liang Yi

AU - Tang, Chieh Ju C.

AU - Hsu, Wen Bin

AU - Wu, Hsin Yi

AU - Liao, Pao Chi

AU - Tang, Tang K.

N1 - Funding Information: We thank Sheau-Hu Chen for technical assistance. This work was supported by an Academia Sinica Investigator Award and by grants from the Thematic Research Program of Academia Sinica (AS-104-TP-B09-1) and the Ministry of Science and Technology (MOST 103-2321-B-001-059 and NSC 103-2321-B001-024). Publisher Copyright: © 2016 The Authors.

PY - 2016/3/29

Y1 - 2016/3/29

N2 - 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. Chou et al. show that CPAP is essential for proper mitotic progression and maintenance of spindle pole integrity. CPAP is phosphorylated by Aurora-A during mitosis and phosphorylated CPAP coheres PCM proteins and maintains centrosome integrity.

AB - 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. Chou et al. show that CPAP is essential for proper mitotic progression and maintenance of spindle pole integrity. CPAP is phosphorylated by Aurora-A during mitosis and phosphorylated CPAP coheres PCM proteins and maintains centrosome integrity.

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

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