SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis
SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis
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DOI：
10.1016/j.molcel.2008.01.013
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发表时间：
2008-03-28
期刊：
影响因子：
16
通讯作者：
Matunis, Michael J.
中科院分区：
文献类型：
--
作者：
Zhang, Xiang-Dong;Goeres, Jacqueline;Matunis, Michael J.
sumo酰化对无脊椎动物的细胞周期调控至关重要；然而，它在哺乳动物细胞周期中的功能在很大程度上是未知的。哺乳动物表达三种相扑类比：SUMO-1、SUMO-2和SUMO-3 （SUMO-2和SUMO-3有96%相同，被称为SUMO-2/3）。我们发现SUMO-2/3定位于着丝粒和浓缩染色体，而SUMO-1定位于有丝分裂纺锤体和纺锤体中间区，表明SUMO类似物调节哺乳动物细胞中不同的有丝分裂过程。与此一致的是，由于微管运动蛋白CENP-E靶向着丝点的缺陷，SUMOylation的全局抑制导致了前期中期阻滞。CENP-E被SUMO-2/3特异性修饰，并具有SUMO-2/3聚合链结合活性，这是着丝点定位所必需的。我们的研究结果表明，SUMO-1和SUMO-2/3修饰不同的蛋白质调节不同的过程，是哺乳动物细胞周期的关键调节剂。
SUMOylation is essential for cell-cycle regulation in invertebrates; however, its functions during the mammalian cell cycle are largely uncharacterized. Mammals express three SUMO paralogs: SUMO-1, SUMO-2, and SUMO-3 (SUMO-2 and SUMO-3 are 96% identical and referred to as SUMO-2/3). We found that SUMO-2/3 localize to centromeres and condensed chromosomes, whereas SUMO-1 localizes to the mitotic spindle and spindle midzone, indicating that SUMO paralogs regulate distinct mitotic processes in mammalian cells. Consistent with this, global inhibition of SUMOylation caused a prometaphase arrest due to defects in targeting the microtubule motor protein CENP-E to kinetochores. CENP-E was found to be modified specifically by SUMO-2/3 and to possess SUMO-2/3 polymeric chain-binding activity essential for kinetochore localization. Our findings indicate that SUMOylation is a key regulator of the mammalian cell cycle, with SUMO-1 and SUMO-2/3 modification of different proteins regulating distinct processes.