Ubiquitin-proteasome system controls ciliogenesis at the initial step of axoneme extension.
Ubiquitin-proteasome system controls ciliogenesis at the initial step of axoneme extension.
复制标题
DOI：
10.1038/ncomms6081
复制
发表时间：
2014-10-01
影响因子：
16.6
通讯作者：
Inagaki M
中科院分区：
文献类型：
--
作者：
Kasahara K;Kawakami Y;Kiyono T;Yonemura S;Kawamura Y;Era S;Matsuzaki F;Goshima N;Inagaki M
初级纤毛是基于微管的感觉细胞器，在发育和组织稳态过程中组织许多关键信号。纤毛微管双联体，命名为轴丝，是直接从母亲中心粒的远端通过一个多步骤的过程后，细胞周期退出，然而，启动这些事件的指导性信号知之甚少。在这里，我们表明，泛素-蛋白酶体机械删除triplein，纤毛发生的负调节，从母亲的中心粒，从而导致极光-A失活，导致纤毛发生。如果通过用蛋白酶体抑制剂处理或通过表达非泛素化的蛋白酶体突变体（K50/57 R）来稳定中心粒蛋白酶体，则纤毛发生被阻断。从两步全球E3筛选开始，我们已经确定KCTD 17作为Cul 3-RING E3连接酶（CRL 3）的底物衔接子，其聚泛素化E3蛋白。KCTD 17的缺失通过异常的trichoplein-Aurora-A活性在轴丝延伸的初始步骤特异性地阻止纤毛发生。因此，CRL 3-KCTD 17靶向类胡萝卜素蛋白水解以在纤毛发生期间启动轴丝延伸。 初级纤毛的生物发生在细胞周期退出后开始，但其形成的调控步骤尚不清楚。在这里，作者表明，蛋白酶体介导的去除纤毛发生抑制剂，triplein，从母亲中心粒启动纤毛发生的第一步。
Primary cilia are microtubule-based sensory organelles that organize numerous key signals during developments and tissue homeostasis. Ciliary microtubule doublet, named axoneme, is grown directly from the distal end of mother centrioles through a multistep process upon cell cycle exit; however, the instructive signals that initiate these events are poorly understood. Here we show that ubiquitin-proteasome machinery removes trichoplein, a negative regulator of ciliogenesis, from mother centrioles and thereby causes Aurora-A inactivation, leading to ciliogenesis. Ciliogenesis is blocked if centriolar trichoplein is stabilized by treatment with proteasome inhibitors or by expression of non-ubiquitylatable trichoplein mutant (K50/57R). Started from two-stepped global E3 screening, we have identified KCTD17 as a substrate-adaptor for Cul3-RING E3 ligases (CRL3s) that polyubiquitylates trichoplein. Depletion of KCTD17 specifically arrests ciliogenesis at the initial step of axoneme extension through aberrant trichoplein-Aurora-A activity. Thus, CRL3-KCTD17 targets trichoplein to proteolysis to initiate the axoneme extension during ciliogenesis. Biogenesis of the primary cilium begins after cell cycle exit, but the regulatory steps for its formation are poorly defined. Here the authors show that proteasome-mediated removal of the ciliogenesis inhibitor, trichoplein, from mother centrioles initiates the first step of ciliogenesis.
登录
查看更多内容
影响因子：
3.7
作者：
Li W;Bengtson MH;Ulbrich A;Matsuda A;Reddy VA;Orth A;Chanda SK;Batalov S;Joazeiro CA
通讯作者：
Joazeiro CA
影响因子：
11.8
作者：
Kleylein-Sohn, Julia;Westendorf, Jens;Nigg, Erich A.
通讯作者：
Nigg, Erich A.
DOI：
10.1083/jcb.200903066
发表时间：
2009-08-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Huang K;Diener DR;Rosenbaum JL
通讯作者：
Rosenbaum JL
影响因子：
3.7
作者：
Hoh RA;Stowe TR;Turk E;Stearns T
通讯作者：
Stearns T
影响因子：
4.3
作者：
Majumder, Shubhra;Fisk, Harold A.
通讯作者：
Fisk, Harold A.