title: PLK1 phosphorylates mitotic centromere-associated kinesin and promotes its depolymerase activity.
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.
authors.affiliation: Anhui Laboratory of Cellular Dynamics and Chemical Biology, Hefei 230027, China.
authors.forename: Liangyu
authors.initials: L
authors.lastname: Zhang
authors.forename: Hengyi
authors.initials: H
authors.lastname: Shao
authors.forename: Yuejia
authors.initials: Y
authors.lastname: Huang
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.forename: Youjun
authors.initials: Y
authors.lastname: Chu
authors.forename: Hai
authors.initials: H
authors.lastname: Hou
authors.forename: Mei
authors.initials: M
authors.lastname: Zhu
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Fu
authors.forename: Felix
authors.initials: F
authors.lastname: Aikhionbare
authors.forename: Guowei
authors.initials: G
authors.lastname: Fang
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D016547:Kinesins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C091489:KIF2C protein, human