期刊
CURRENT BIOLOGY
卷 23, 期 22, 页码 2255-2261出版社
CELL PRESS
DOI: 10.1016/j.cub.2013.09.019
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资金
- NCI [P30 CA23074]
- GI SPORE [NCI/NIH P50 CA95060]
- National Science Foundation [1158151]
- Arizona Biomedical Research Commission [1210]
- TRIF Imaging Fellowship Program
- Division of Intramural Research at the NIH/NHLBI [1ZIAHL006104]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1158151] Funding Source: National Science Foundation
Polo-like kinase 4 (Plk4) is a conserved master regulator of centriole assembly [1]. Previously, we found that Drosophila Plk4 protein levels are actively suppressed during interphase [2]. Degradation of interphase Plk4 prevents centriole overduplication and is mediated by the ubiquitin-ligase complex SCFSlimb/beta TrCP [3, 4]. Since Plk4 stability depends on its activity [5, 6], we studied the consequences of inactivating Plk4 or perturbing its phosphorylation state within its Slimb-recognition motif (SRM). Mass spectrometry of in-vitro-phosphorylated Plk4 and Plk4 purified from cells reveals that it is directly responsible for extensively autophosphorylating and generating its Slimb-binding phosphodegron. Phosphorylatable residues within this regulatory region were systematically mutated to determine their impact on Plk4 protein levels and centriole duplication when expressed in S2 cells. Notably, autophosphorylation of a single residue (Ser293) within the SRM is critical for Slimb binding and ubiquitination. Our data also demonstrate that autophosphorylation of numerous residues flanking S293 collectively contribute to establishing a high-affinity binding site for SCFSlimb. Taken together, our findings suggest that Plk4 directly generates its own phosphodegron and can do so without the assistance of an additional kinase(s).
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