title: NudC is required for Plk1 targeting to the kinetochore and chromosome congression.
abstract: The equal distribution of chromosomes during mitosis is critical for maintaining the integrity of the genome. Essential to this process are the capture of spindle microtubules by kinetochores and the congression of chromosomes to the metaphase plate . Polo-like kinase 1 (Plk1) is a mitotic kinase that has been implicated in microtubule-kinetochore attachment, tension generation at kinetochores, tension-responsive signal transduction, and chromosome congression . The tension-sensitive substrates of Plk1 at the kinetochore are unknown. Here, we demonstrate that human Nuclear distribution protein C (NudC), a 42 kDa protein initially identified in Aspergillus nidulans and shown to be phosphorylated by Plk1 , plays a significant role in regulating kinetochore function. Plk1-phosphorylated NudC colocalizes with Plk1 at the outer plate of the kinetochore. Depletion of NudC reduced end-on microtubule attachments at kinetochores and resulted in defects in chromosome congression at the metaphase plate. Importantly, NudC-deficient cells exhibited mislocalization of Plk1 and the Kinesin-7 motor CENP-E from prometaphase kinetochores. Ectopic expression of wild-type NudC, but not NudC containing mutations in the Plk1 phosphorylation sites, recovered Plk1 localization at the kinetochore and rescued chromosome congression. Thus, NudC functions as both a substrate and a spatial regulator of Plk1 at the kinetochore to promote chromosome congression.
authors.affiliation: Program in Cell and Molecular Biology, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Michiya
authors.initials: M
authors.lastname: Nishino
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kurasawa
authors.forename: Randall
authors.initials: R
authors.lastname: Evans
authors.forename: Sue-Hwa
authors.initials: SH
authors.lastname: Lin
authors.forename: Bill R
authors.initials: BR
authors.lastname: Brinkley
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Yu-Lee
mesh_terms: D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D045584:Chromosome Positioning; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D008677:Metaphase / Q000235:genetics*; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C512648:NUDC protein, human; C068688:centromere protein E