CENP-U cooperates with Hec1 to orchestrate kinetochore-microtubule attachment

J Biol Chem. 2011 Jan 14;286(2):1627-38. doi: 10.1074/jbc.M110.174946. Epub 2010 Nov 5.

Abstract

Mitosis is an orchestration of dynamic interaction between chromosomes and spindle microtubules by which genomic materials are equally distributed into two daughter cells. Previous studies showed that CENP-U is a constitutive centromere component essential for proper chromosome segregation. However, the precise molecular mechanism has remained elusive. Here, we identified CENP-U as a novel interacting partner of Hec1, an evolutionarily conserved kinetochore core component essential for chromosome plasticity. Suppression of CENP-U by shRNA resulted in mitotic defects with an impaired kinetochore-microtubule attachment. Interestingly, CENP-U not only binds microtubules directly but also displays a cooperative microtubule binding activity with Hec1 in vitro. Furthermore, we showed that CENP-U is a substrate of Aurora-B. Importantly, phosphorylation of CENP-U leads to reduced kinetochore-microtubule interaction, which contributes to the error-correcting function of Aurora-B. Taken together, our results indicate that CENP-U is a novel microtubule binding protein and plays an important role in kinetochore-microtubule attachment through its interaction with Hec1.

Publication types

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

MeSH terms

  • Aurora Kinase B
  • Aurora Kinases
  • Cell Cycle Proteins
  • Chromosome Segregation / physiology*
  • Cytoskeletal Proteins
  • HeLa Cells
  • Histones
  • Humans
  • Kinetochores / physiology*
  • Microtubules / physiology*
  • Nuclear Proteins / physiology*
  • Phosphorylation / physiology
  • Protein Serine-Threonine Kinases / metabolism

Substances

  • CENPU protein, human
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Histones
  • NDC80 protein, human
  • Nuclear Proteins
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases