Institute of Biochemistry, Swiss Federal Institute of Technology Zurich, CH-8093 Zurich, Switzerland.
J Cell Biol. 2009 Dec 14;187(6):791-800. doi: 10.1083/jcb.200906117.
Cul3 (Cullin3)-based E3 ubiquitin ligases recently emerged as critical regulators of mitosis. In this study, we identify two mammalian BTB (Bric-a-brac-Tramtrack-Broad complex)-Kelch proteins, KLHL21 and KLHL22, that interact with Cul3 and are required for efficient chromosome alignment. Interestingly, KLHL21 but not KLHL22 is necessary for cytokinesis and regulates translocation of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase, similar to the previously described BTB-Kelch proteins KLHL9 and KLHL13. KLHL21 directly binds to aurora B and mediates ubiquitination of aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules in anaphase and recruits aurora B and Cul3 to this region. Together, our results suggest that different Cul3 adaptors nonredundantly regulate aurora B during mitosis, possibly by ubiquitinating different pools of aurora B at distinct subcellular localizations.
Cul3(Cullin3)基 E3 泛素连接酶最近被确定为有丝分裂的关键调节因子。在这项研究中,我们鉴定了两种哺乳动物 BTB(Bric-a-brac-Tramtrack-Broad complex-Kelch 复合物)-Kelch 蛋白 KLHL21 和 KLHL22,它们与 Cul3 相互作用,并且对于有效的染色体对齐是必需的。有趣的是,KLHL21 但不是 KLHL22 对于胞质分裂是必需的,并且在后期将染色体乘客复合物(CPC)从染色体转移到纺锤体中部区,类似于先前描述的 BTB-Kelch 蛋白 KLHL9 和 KLHL13。KLHL21 直接与 Aurora B 结合,并在体外介导 Aurora B 的泛素化。与 KLHL9 和 KLHL13 不同,KLHL21 在后期定位于中部微管,并将 Aurora B 和 Cul3 募集到该区域。总之,我们的结果表明,不同的 Cul3 接头在有丝分裂过程中非冗余地调节 Aurora B,可能通过在不同的亚细胞定位上泛素化不同的 Aurora B 池来实现。