期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 7, 页码 E657-E666出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1417967112
关键词
autoinhibition; centriole; centrosome; Polo box; Polo-like kinase 4
资金
- National Cancer Institute (NCI) Grant [P30 CA23074]
- NCI/NIH Gastrointestinal Specialized Programs of Research Excellence Grant [P50 CA95060]
- National Science Foundation Grant [1158151]
- Arizona Biomedical Research Commission Grant [1210]
- Phoenix Friends
- Division of Intramural Research at the NIH/National Heart, Lung, and Blood Institute Project [1ZIAHL006104]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1158151] Funding Source: National Science Foundation
Polo-like kinase 4 (Plk4) is a master regulator of centriole duplication, and its hyperactivity induces centriole amplification. Homodimeric Plk4 has been shown to be ubiquitinated as a result of autophosphorylation, thus promoting its own degradation and preventing centriole amplification. Unlike other Plks, Plk4 contains three rather than two Polo box domains, and the function of its third Polo box (PB3) is unclear. Here, we performed a functional analysis of Plk4's structural domains. Like other Plks, Plk4 possesses a previously unidentified autoinhibitory mechanism mediated by a linker (L1) near the kinase domain. Thus, autoinhibition is a conserved feature of Plks. In the case of Plk4, autoinhibition is relieved after homodimerization and is accomplished by PB3 and by autophosphorylation of L1. In contrast, autophosphorylation of the second linker promotes separation of the Plk4 homodimer. Therefore, autoinhibition delays the multiple consequences of activation until Plk4 dimerizes. These findings reveal a complex mechanism of Plk4 regulation and activation which govern the process of centriole duplication.
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