Mitotic Regulation of the Stability of Microtubule Plus-end Tracking Protein EB3 by Ubiquitin Ligase SIAH-1 and Aurora Mitotic Kinases
Mitotic Regulation of the Stability of Microtubule Plus-end Tracking Protein EB3 by Ubiquitin Ligase SIAH-1 and Aurora Mitotic Kinases
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DOI：
10.1074/jbc.m109.000273
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发表时间：
2009-10-09
影响因子：
4.8
通讯作者：
Urano, Takeshi
中科院分区：
文献类型：
--
作者：
Ban, Reiko;Matsuzaki, Hideki;Urano, Takeshi
微管加末端跟踪蛋白（+TIPs）控制微管动力学的基本过程，如细胞周期，细胞内运输和细胞运动，但如何+TIPs在有丝分裂过程中的调节仍不清楚。在这里，我们表明，内源性末端结合蛋白家族EB3是稳定的有丝分裂过程中，促进细胞周期的进程在前中期，然后在过渡到G，阶段下调。泛素-蛋白质异肽连接酶SIAH-1促进EB3多聚泛素化和随后的蛋白酶体介导的降解，而SIAH-1敲低增加EB3稳定性和稳态水平。两种有丝分裂激酶Aurora-A和Aurora-B在Ser-176处磷酸化内源性EB3，并且磷酸化触发EB3-SIAH-1复合物的破坏，导致有丝分裂期间EB3稳定。我们的研究结果提供了新的见解+TIPs在细胞周期转换的调节机制。
Microtubule plus-end tracking proteins (+TIPs) control microtubule dynamics in fundamental processes such as cell cycle, intracellular transport, and cell motility, but how +TIPs are regulated during mitosis remains largely unclear. Here we show that the endogenous end-binding protein family EB3 is stable during mitosis, facilitates cell cycle progression at prometaphase, and then is down-regulated during the transition to G, phase. The ubiquitin-protein isopeptide ligase SIAH-1 facilitates EB3 polyubiquitination and subsequent proteasome-mediated degradation, whereas SIAH-1 knockdown increases EB3 stability and steady-state levels. Two mitotic kinases, Aurora-A and Aurora-B, phosphorylate endogenous EB3 at Ser-176, and the phosphorylation triggers disruption of the EB3-SIAH-1 complex, resulting in EB3 stabilization during mitosis. Our results provide new insight into a regulatory mechanism of +TIPs in cell cycle transition.