NudC is required for Plk1 targeting to the kinetochore and chromosome congression

Curr Biol. 2006 Jul 25;16(14):1414-21. doi: 10.1016/j.cub.2006.05.052.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle Proteins / physiology*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Positioning
  • Humans
  • Kinetochores / metabolism*
  • Kinetochores / ultrastructure
  • Metaphase / genetics*
  • Microtubules / metabolism
  • Models, Biological
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Phosphorylation
  • Protein Transport
  • Protein-Serine-Threonine Kinases / analysis
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA Interference

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • NUDC protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • centromere protein E
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1