Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B

Science. 2010 Oct 8;330(6001):235-9. doi: 10.1126/science.1189505. Epub 2010 Aug 12.

Abstract

A hallmark of mitosis is the appearance of high levels of histone phosphorylation, yet the roles of these modifications remain largely unknown. Here, we demonstrate that histone H3 phosphorylated at threonine 3 is directly recognized by an evolutionarily conserved binding pocket in the BIR domain of Survivin, which is a member of the chromosomal passenger complex (CPC). This binding mediates recruitment of the CPC to chromosomes and the resulting activation of its kinase subunit Aurora B. Consistently, modulation of the kinase activity of Haspin, which phosphorylates H3T3, leads to defects in the Aurora B-dependent processes of spindle assembly and inhibition of nuclear reformation. These findings establish a direct cellular role for mitotic histone H3T3 phosphorylation, which is read and translated by the CPC to ensure accurate cell division.

Publication types

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

MeSH terms

  • Animals
  • Aurora Kinases
  • Cell Division
  • Centromere / metabolism
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes / metabolism*
  • Enzyme Activation
  • Histones / metabolism*
  • Mitosis*
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein-Serine-Threonine Kinases / metabolism*
  • Spindle Apparatus / metabolism
  • Survivin
  • Threonine / metabolism
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / metabolism*
  • Xenopus laevis

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Histones
  • INCENP protein, Xenopus
  • Survivin
  • Xenopus Proteins
  • birc5.2 protein, Xenopus
  • cdca9 protein, Xenopus
  • survivin protein, Xenopus laevis
  • Threonine
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • haspin protein, Xenopus laevis

Associated data

  • GENBANK/HM559585