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首页> 外文期刊>Current Biology: CB >Polo-like Kinase 4 Autodestructs by Generating Its Slimb-Binding Phosphodegron
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Polo-like Kinase 4 Autodestructs by Generating Its Slimb-Binding Phosphodegron

机译：Polo样激酶4通过生成Slimb-binding Phosphodegron来自毁。

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摘要

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).
机译：马球样激酶4（Plk4）是中心粒装配的保守主调节子[1]。以前，我们发现果蝇Plk4蛋白水平在相间期被积极抑制[2]。间期Plk4的降解可防止中心体重复复制，并由泛素-连接酶复合物SCFSlimb / beta TrCP介导[3，4]。由于Plk4的稳定性取决于其活性[5，6]，我们研究了在Slimb识别基序（SRM）中失活Plk4或扰乱其磷酸化状态的后果。体外磷酸化的Plk4和从细胞中纯化的Plk4的质谱分析表明，它直接负责广泛的自磷酸化并产生其Slimb结合的磷酸脱氢子。系统调节此调节区内的可磷酸化残基，以确定它们在S2细胞中表达时对Plk4蛋白质水平和中心粒重复的影响。值得注意的是，SRM中单个残基（Ser293）的自磷酸化对于Slimb结合和泛素化至关重要。我们的数据还证明，S293侧翼的许多残基的自磷酸化共同有助于建立SCFSlimb的高亲和力结合位点。综上所述，我们的发现表明，Plk4直接产生其自身的磷酸腺嘌呤，并且可以在没有其他激酶协助的情况下做到这一点。

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