Methylation-mediated control of aurora kinase B and Haspin with epigenetically modified histone H3 N-terminal peptides

Bioorg Med Chem. 2011 Apr 1;19(7):2373-7. doi: 10.1016/j.bmc.2011.02.011. Epub 2011 Feb 18.

Abstract

If multiple post-translational modifications are responsible for important biological markers, additional specificity must be present to serve as embedded combinatorial markers for phosphorylation. In this investigation, we have attempted to elucidate the specificity of AURKB and Haspin by using peptides of various lengths that contain all possible methylations, acetylations, and phosphorylations in histone H3 N-terminal peptides. The activity of AURKB is affected by a wide range of modifications from R2 to K14, while that of Haspin is affected significantly by modifications at R2 and K4. In cases where kinase activity is reduced substantially by other modifications, dimethylation at R2 and R8 totally abolishes phosphorylation at S10 promoted by AURKB and as does dimethylation at R2 on Haspin promoted phosphorylation at T3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Aurora Kinase B
  • Aurora Kinases
  • Epigenomics
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Methylation
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Peptide Fragments
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • HASPIN protein, human
  • Protein Serine-Threonine Kinases