The activity regulation of the mitotic centromere-associated kinesin by Polo-like kinase 1
The activity regulation of the mitotic centromere-associated kinesin by Polo-like kinase 1
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DOI：
10.18632/oncotarget.2843
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发表时间：
2015-03-30
期刊：
影响因子：
--
通讯作者：
Yuan, Juping
中科院分区：
文献类型：
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作者：
Ritter, Andreas;Sanhaji, Mourad;Yuan, Juping
有丝分裂着丝粒相关驱动蛋白（MCAK）是一种有效的微管解聚酶，参与调控微管动力学。MCAK的活性和亚细胞定位受到关键的有丝分裂激酶的严格调节，如Polo样激酶1（Plk 1）通过磷酸化MCAK中的多个残基。由于Plk 1在不同阶段磷酸化底物的不同残基，我们已经解剖了Plk 1对MCAK的磷酸化，并更深入地表征了其功能。我们最近发现，MCAK中的S621是Plk 1的主要磷酸化位点，Plk 1负责通过促进MCAK与APC/C-Cdc 20的结合来调节MCAK的降解。在本研究中，我们已经解决了另外两个残基的Plk 1磷酸化，即S632/S633在C-末端的MCAK。我们的数据表明，Plk 1磷酸化S632/S633，并调节其在有丝分裂中的催化活性。在有丝分裂的早期阶段，这种磷酸化是正确的纺锤体组装所必需的。随后S632/S633的去磷酸化可能是及时将染色体排列到中期平板上所必需的。因此，我们的研究提出了Plk 1调节MCAK的新机制：在有丝分裂中，MCAK的降解由S621上的Plk 1磷酸化控制，而其活性由S632/S633上的Plk 1磷酸化调节。
The mitotic centromere-associated kinesin (MCAK), a potent microtubule depolymerase, is involved in regulating microtubule dynamics. The activity and subcellular localization of MCAK are tightly regulated by key mitotic kinases, such as Polo-like kinase 1 (Plk1) by phosphorylating multiple residues in MCAK. Since Plk1 phosphorylates very often different residues of substrates at different stages, we have dissected individual phosphorylation of MCAK by Plk1 and characterized its function in more depth. We have recently shown that S621 in MCAK is the major phosphorylation site of Plk1, which is responsible for regulating MCAK's degradation by promoting the association of MCAK with APC/C-Cdc20. In the present study, we have addressed another two residues phosphorylated by Plk1, namely S632/S633 in the C-terminus of MCAK. Our data suggest that Plk1 phosphorylates S632/S633 and regulates its catalytic activity in mitosis. This phosphorylation is required for proper spindle assembly during early phases of mitosis. The subsequent dephosphorylation of S632/S633 might be necessary to timely align the chromosomes onto the metaphase plate. Therefore, our studies suggest new mechanisms by which Plk1 regulates MCAK: the degradation of MCAK is controlled by Plk1 phosphorylation on S621, whereas its activity is modulated by Plk1 phosphorylation on S632/S633 in mitosis.