Temporal changes in Hec1 phosphorylation control kinetochore-microtubule attachment stability during mitosis

J Cell Sci. 2011 Feb 15;124(Pt 4):622-34. doi: 10.1242/jcs.072629. Epub 2011 Jan 25.

Abstract

Precise control of the attachment strength between kinetochores and spindle microtubules is essential to preserve genomic stability. Aurora B kinase has been implicated in regulating the stability of kinetochore-microtubule attachments but its relevant kinetochore targets in cells remain unclear. Here, we identify multiple serine residues within the N-terminus of the kinetochore protein Hec1 that are phosphorylated in an Aurora-B-kinase-dependent manner during mitosis. On all identified target sites, Hec1 phosphorylation at kinetochores is high in early mitosis and decreases significantly as chromosomes bi-orient. Furthermore, once dephosphorylated, Hec1 is not highly rephosphorylated in response to loss of kinetochore-microtubule attachment or tension. We find that a subpopulation of Aurora B kinase remains localized at the outer kinetochore even upon Hec1 dephosphorylation, suggesting that Hec1 phosphorylation by Aurora B might not be regulated wholly by spatial positioning of the kinase. Our results define a role for Hec1 phosphorylation in kinetochore-microtubule destabilization and error correction in early mitosis and for Hec1 dephosphorylation in maintaining stable attachments in late mitosis.

Publication types

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

MeSH terms

  • Aurora Kinase B
  • Aurora Kinases
  • Cytoskeletal Proteins
  • HeLa Cells
  • Humans
  • Kinetochores / chemistry
  • Kinetochores / metabolism*
  • Microtubules / chemistry
  • Microtubules / genetics
  • Microtubules / metabolism*
  • Mitosis*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Stability
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism

Substances

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