Plk1 Regulates the kinesin-13 Protein Kif2b to Promote Faithful Chromosome Segregation

Mol Biol Cell. 2012 Jun;23(12):2264-74. doi: 10.1091/mbc.E11-12-1013. Epub 2012 Apr 25.

Abstract

Solid tumors are frequently aneuploid, and many display high rates of ongoing chromosome missegregation in a phenomenon called chromosomal instability (CIN). The most common cause of CIN is the persistence of aberrant kinetochore-microtubule (k-MT) attachments, which manifest as lagging chromosomes in anaphase. k-MT attachment errors form during prometaphase due to stochastic interactions between kinetochores and microtubules. The kinesin-13 protein Kif2b promotes the correction of k-MT attachment errors in prometaphase, but the mechanism restricting this activity to prometaphase remains unknown. Using mass spectrometry, we identified multiple phosphorylation sites on Kif2b, some of which are acutely sensitive to inhibition of Polo-like kinase 1 (Plk1). We show that Plk1 directly phosphorylates Kif2b at threonine 125 (T125) and serine 204 (S204), and that these two sites differentially regulate Kif2b function. Phosphorylation of S204 is required for the kinetochore localization and activity of Kif2b in prometaphase, and phosphorylation of T125 is required for Kif2b activity in the correction of k-MT attachment errors. These data demonstrate that Plk1 regulates both the localization and activity of Kif2b during mitosis to promote the correction of k-MT attachment errors to ensure mitotic fidelity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Chromosome Segregation*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunoblotting
  • Kinesin / genetics
  • Kinesin / metabolism*
  • Kinetochores / metabolism
  • Mass Spectrometry
  • Microscopy, Fluorescence
  • Microtubules / metabolism
  • Mitosis*
  • Mutation
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Serine / genetics
  • Serine / metabolism
  • Threonine / genetics
  • Threonine / metabolism

Substances

  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • Green Fluorescent Proteins
  • Threonine
  • Serine
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • KIF2B protein, human
  • Kinesin