期刊
JOURNAL OF CELL SCIENCE
卷 123, 期 13, 页码 2163-2169出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.068502
关键词
Plk4; Autophosphorylation; beta TrCP; Centriole duplication
类别
资金
- Max-Planck Society
- Boehringer Ingelheim Fonds
Centrioles are the main constituents of the mammalian centrosome and act as basal bodies for ciliogenesis. Centrosomes organize the cytoplasmic microtubule network during interphase and the mitotic spindle during mitosis, and aberrations in centrosome number have been implicated in chromosomal instability and tumor formation. The centriolar protein Polo-like kinase 4 (Plk4) is a key regulator of centriole biogenesis and is crucial for maintaining constant centriole number, but the mechanisms regulating its activity and expression are only beginning to emerge. Here, we show that human Plk4 is subject to beta TrCP-dependent proteasomal degradation, indicating that this pathway is conserved from Drosophila to human. Unexpectedly, we found that stable overexpression of kinase-dead Plk4 leads to centriole overduplication. This phenotype depends on the presence of endogenous wild-type Plk4. Our data indicate that centriole overduplication results from disruption of Plk4 trans-autophosphorylation by kinase-dead Plk4, which then shields endogenous Plk4 from recognition by beta TrCP. We conclude that active Plk4 promotes its own degradation by catalyzing beta TrCP binding through trans-autophosphorylation (phosphorylation by the other kinase in the dimer) within homodimers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据