RanBP2 and SENP3 Function in a Mitotic SUMO2/3 Conjugation-Deconjugation Cycle on Borealin
RanBP2 and SENP3 Function in a Mitotic SUMO2/3 Conjugation-Deconjugation Cycle on Borealin
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DOI：
10.1091/mbc.e08-05-0511
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发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Muller, Stefan
中科院分区：
文献类型：
--
作者：
Klein, Ulf R.;Haindl, Markus;Muller, Stefan
泛素样的SUMO系统控制着细胞的关键功能，一些证据表明SUMO在有丝分裂过程中起着关键作用。然而，在哺乳动物细胞中，有丝分裂的聚合化底物和相关的调控成分并没有很好地定义。在这里，我们确定了Borealin，染色体乘客复合体（CPC）的一个组成部分，作为SUMO的有丝分裂靶标。CPC，另外包括INCENP， Survivin和Aurora B，调节关键的有丝分裂事件，包括染色体聚集，纺锤体组装检查点和细胞质分裂。我们发现Borealin优先被SUMO2/3修饰，并且这种修饰在有丝分裂过程中受到动态调节，在有丝分裂早期达到峰值。有趣的是，SUMO连接酶RanBP2与CPC相互作用，在体外刺激Borealin的SUMO修饰，并且是其在体内修饰所必需的。此外，SUMO异肽酶SENP3是Borealin的特异性相互作用伙伴，并催化从Borealin中去除SUMO2/3。因此，这些数据描绘了Borealin的有丝分裂SUMO2/3偶联-去偶联周期，并进一步确定了RanBP2和SENP3在有丝分裂SUMO途径中的调节功能。
The ubiquitin-like SUMO system controls cellular key functions, and several lines of evidence point to a critical role of SUMO for mitotic progression. However, in mammalian cells mitotic substrates of sumoylation and the regulatory components involved are not well defined. Here, we identify Borealin, a component of the chromosomal passenger complex (CPC), as a mitotic target of SUMO. The CPC, which additionally comprises INCENP, Survivin, and Aurora B, regulates key mitotic events, including chromosome congression, the spindle assembly checkpoint, and cytokinesis. We show that Borealin is preferentially modified by SUMO2/3 and demonstrate that the modification is dynamically regulated during mitotic progression, peaking in early mitosis. Intriguingly, the SUMO ligase RanBP2 interacts with the CPC, stimulates SUMO modification of Borealin in vitro, and is required for its modification in vivo. Moreover, the SUMO isopeptidase SENP3 is a specific interaction partner of Borealin and catalyzes the removal of SUMO2/3 from Borealin. These data thus delineate a mitotic SUMO2/3 conjugation-deconjugation cycle of Borealin and further assign a regulatory function of RanBP2 and SENP3 in the mitotic SUMO pathway.