去泛素化酶 USP9X 通过稳定中心体周围物质 1 蛋白来维持中心粒卫星的完整性。
Deubiquitylase USP9X maintains centriolar satellite integrity by stabilizing pericentriolar material 1 protein.
机构信息
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Departments of Structural Biology and Developmental Neurobiology, St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
出版信息
J Cell Sci. 2019 Jan 22;132(2):jcs221663. doi: 10.1242/jcs.221663.
Centriolar satellites are small cytoplasmic granules that play important roles in regulating the formation of centrosomes and primary cilia. Ubiquitylation of satellite proteins, including the core satellite scaffold protein pericentriolar material 1 (PCM1), regulates centriolar satellite integrity. Currently, deubiquitylases that control centriolar satellite integrity have not been identified. In this study, we find that the deubiquitylase USP9X binds PCM1, and antagonizes PCM1 ubiquitylation to protect it from proteasomal degradation. Knockdown of USP9X in human cell lines reduces PCM1 protein levels, disrupts centriolar satellite particles and causes localization of satellite proteins, such as CEP290, to centrosomes. Interestingly, knockdown of mindbomb 1 (MIB1), a ubiquitin ligase that promotes PCM1 ubiquitylation and degradation, in USP9X-depleted cells largely restores PCM1 protein levels and corrects defects caused by the loss of USP9X. Overall, our study reveals that USP9X is a constituent of centriolar satellites and functions to maintain centriolar satellite integrity by stabilizing PCM1.
中心体卫星是一种小型细胞质颗粒，在调节中心体和初级纤毛的形成中发挥着重要作用。卫星蛋白的泛素化，包括核心卫星支架蛋白中心体基质蛋白 1（PCM1），调节着中心体卫星的完整性。目前，控制中心体卫星完整性的去泛素化酶尚未被鉴定。在这项研究中，我们发现去泛素酶 USP9X 与 PCM1 结合，并拮抗 PCM1 的泛素化，从而保护其免受蛋白酶体降解。在人细胞系中敲低 USP9X 会降低 PCM1 蛋白水平，破坏中心体卫星颗粒，并导致卫星蛋白如 CEP290 定位于中心体。有趣的是，在 USP9X 耗尽的细胞中敲低泛素连接酶 mindbomb 1（MIB1），可大大恢复 PCM1 蛋白水平，并纠正因 USP9X 缺失而引起的缺陷。总的来说，我们的研究揭示了 USP9X 是中心体卫星的组成部分，通过稳定 PCM1 来维持中心体卫星的完整性。
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