A mitotic kinase TOPK enhances cdk1/cyclin B1-dependent phosphorylation of PRC1 and promotes cytokinesis
A mitotic kinase TOPK enhances cdk1/cyclin B1-dependent phosphorylation of PRC1 and promotes cytokinesis
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DOI：
10.1016/j.jmb.2007.04.067
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发表时间：
2007-07-06
影响因子：
5.6
通讯作者：
Kito, Katsumi
中科院分区：
文献类型：
--
作者：
Abe, Yasuhito;Takeuchi, Takashi;Kito, Katsumi
MAPKK 样有丝分裂激酶 TOPK 意味着有丝分裂纺锤体和纺锤体中区的形成并完成胞质分裂，但其潜在机制仍不清楚。微管成束蛋白 PRC1 在有丝分裂纺锤体和纺锤体中区的形成中起着关键作用。由于它们的功能相似，我们试图阐明这两个分子之间的联系。 TOPK 通过 PRCL 的 cdk1/cyclin B1 依赖性磷酸化支持有丝分裂进展。 TOPK 在体内诱导 PRC1 在 T481 磷酸化，然而，TOPK 在体外不会磷酸化 PRC1。仅当cdk1/cyclin B1在体外同时存在时，TOPK才会诱导PRC1在T481位点的磷酸化。 TOPK 的酶活性和 TOPK 与 PRC1 的结合能力对于这种磷酸化都是必需的。 TOPK 通过其靠近 C 末端的独特区域与 cdk1/ 细胞周期蛋白 B1、微管和 PRC1 结合。 TOPK 在体内整个细胞周期中与 cdk1 紧密共定位。总的来说，这些数据表明，TOPK在有丝分裂期间与n-dcrotubule上的cdk1/细胞周期蛋白B1和PRC1形成激酶-底物复合物，增强了PRC1的cdk1/细胞周期蛋白B1依赖性磷酸化，从而强烈促进胞质分裂。 (c) 2007 Elsevier Ltd. 保留所有权利。
A MAPKK-like mitotic kinase, TOPK, implies the formation of mitotic spindles and spindle midzone and accomplishing cytokinesis, however, its underlying mechanism remains unclear. A microtubule bundling protein, PRC1, plays a pivotal role in the formation of mitotic spindles and spindle midzone. Because of their functional resemblance, we attempted to clarify the links between these two molecules. TOPK supported mitotic advance via the cdk1/cyclin B1-dependent phosphorylation of PRCL TOPK induced the phosphorylation of PRC1 at T481 in vivo, however, TOPK did not phosphorylate PRC1 in vitro. TOPK induced the phosphorylation of PRC1 at T481 only when the cdk1/cyclin B1 existed simultaneously in vitro. Both the enzymatic activity of TOPK and association competence of TOPK with PRC1 were mandatory for this phosphorylation. TOPK binds to cdk1/ cyclin B1, microtubules and PRC1 via its unique region near the C terminus. TOPK co-localized closely with cdk1 throughout the cell cycle in vivo. Collectively, these data indicate that TOPK, which makes a kinase-substrate complex with cdkl/cyclin B1 and PRC1 on n-dcrotubules during mitosis, enhances the cdkl/cyclin B1-dependent phosphorylation of PRC1 and thereby strongly promotes cytokinesis. (c) 2007 Elsevier Ltd. All rights reserved.