2011年1月28日,我室生物大分子结构与功能研究部姚雪彪教授研究组在JOURNAL OF BIOLOGICAL CHEMISTRY上发表题为PLK1 Phosphorylates Mitotic Centromere-associated Kinesin and Promotes Its Depolymerase Activity的论文。
Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 286 Issue: 4 Pages: 3033-3046 Published: JAN 28 2011
Zhang LY (Zhang, Liangyu)2, Shao HY (Shao, Hengyi), Huang YJ (Huang, Yuejia)2, Yan F (Yan, Feng)2, Chu YJ (Chu, Youjun), Hou H (Hou, Hai), Zhu M (Zhu, Mei), Fu CH (Fu, Chuanhai)2, Aikhionbare F (Aikhionbare, Felix)2, Fang GW (Fang, Guowei)1, Ding X (Ding, Xia)3, Yao XBA (Yao, Xuebiao)1,2
Addresses:
1. Hefei Natl Lab Phys Sci Nanoscale, Anhui Lab Cellular Dynam & Chem Biol, Hefei 230027, Peoples R China
2. Morehouse Sch Med, Dept Physiol, Atlanta, GA 30310 USA
3. Beijing Univ Chinese Med, Dept Med, Beijing 100029, Peoples R China
E-mail Addresses: yaoxb@ustc.edu.cn
Reprint Address: Yao, XBA (reprint author), Hefei Natl Lab Phys Sci Nanoscale, Anhui Lab Cellular Dynam & Chem Biol, Hefei 230027, Peoples R China
Abstract:
During cell division, interaction between kinetochores and dynamic spindle microtubules governs chromosome movements. The microtubule depolymerase mitotic centromere-associated kinesin (MCAK) is a key regulator of mitotic spindle assembly and dynamics. However, the regulatory mechanisms underlying its depolymerase activity during the cell cycle remain elusive. Here, we showed that PLK1 is a novel regulator of MCAK in mammalian cells. MCAK interacts with PLK1 in vitro and in vivo. The neck and motor domain of MCAK associates with the kinase domain of PLK1. MCAK is a novel substrate of PLK1, and the phosphorylation stimulates its microtubule depolymerization activity of MCAK in vivo. Overexpression of a polo-like kinase 1 phosphomimetic mutant MCAK causes a dramatic increase in misaligned chromosomes and in multipolar spindles in mitotic cells, whereas overexpression of a nonphosphorylatable MCAK mutant results in aberrant anaphase with sister chromatid bridges, suggesting that precise regulation of the MCAK activity by PLK1 phosphorylation is critical for proper microtubule dynamics and essential for the faithful chromosome segregation. We reasoned that dynamic regulation of MCAK phosphorylation by PLK1 is required to orchestrate faithful cell division, whereas the high levels of PLK1 and MCAK activities seen in cancer cells may account for a mechanism underlying the pathogenesis of genomic instability.