A Cul3-based E3 ligase removes aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells
A Cul3-based E3 ligase removes aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells
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DOI：
10.1016/j.devcel.2007.03.019
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发表时间：
2007-06-01
影响因子：
11.8
通讯作者：
Peter, Matthias
中科院分区：
文献类型：
--
作者：
Sumara, Izabela;Quadroni, Manfredo;Peter, Matthias
忠实的细胞周期进程受到泛素-蛋白酶体系统的严格控制。在这里，我们鉴定了一种基于cullin 3的人类E3连接酶(CUL3)，它是有丝分裂所必需的。在具有底物特异性接头KLHL9和KLHL13的复合体中，CUL3是染色体在中期正确排列、正确的中带和中体形成以及细胞质分裂完成所必需的。这种基于CUL3的E3连接酶从有丝分裂染色体上移除染色体乘客复合体的成分，并允许它们在后期积累在中心纺锤体上。Aurora B在体外直接与KLHL9和KLHL13的底物识别结构域结合，并在有丝分裂过程中与CUL3复合体共沉淀。此外，Aurora B在体内以依赖于CUL3的方式泛素化，在体外通过重组的CUL3/KLHL9/KLHL13连接酶进行泛素化。因此，我们认为CUL3/KLHL9/KLHL13 E3连接酶控制Aurora B在有丝分裂染色体上的动态行为，从而协调忠诚的有丝分裂进程和细胞质分裂的完成。
Faithful cell-cycle progression is tightly controlled by the ubiquitin-proteasome system. Here we identify a human Cullin 3-based E3 ligase (Cul3) which is essential for mitotic division. In a complex with the substrate-specific adaptors KLHL9 and KLHL13, Cul3 is required for correct chromosome alignment in metaphase, proper midzone and midbody formation, and completion of cytokinesis. This Cul3-based E3 ligase removes components of the chromosomal passenger complex from mitotic chromosomes and allows their accumulation on the central spindle during anaphase. Aurora B directly binds to the substrate-recognition domain of KLHL9 and KLHL13 in vitro, and coimmunoprecipitates with the Cul3 complex during mitosis. Moreover, Aurora B is ubiquitylated in a Cul3-dependent manner in vivo, and by reconstituted Cul3/KLHL9/KLHL13 ligase in vitro. We thus propose that the Cul3/KLHL9/KLHL13 E3 ligase controls the dynamic behavior of Aurora B on mitotic chromosomes, and thereby coordinates faithful mitotic progression and completion of cytokinesis.