Akt kinase targets the association of CBP with histone H3 to regulate the acetylation of lysine K18

FEBS Lett. 2013 Apr 2;587(7):847-53. doi: 10.1016/j.febslet.2013.02.023. Epub 2013 Feb 19.

Abstract

CREB binding protein (CBP) is an acetyltransferase that plays an important role in many biological processes. Here, we show that Akt phosphorylates CBP at threonine 1871 and suppresses its acetyltransferase activity by impeding the binding of CBP to histone H3, which results in a decrease in lysine K18 acetylation and dysregulation of target genes. Our results demonstrate that Akt regulates acetyltransferase activity through CBP phosphorylation, which may contribute to tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Blotting, Western
  • CREB-Binding Protein / genetics
  • CREB-Binding Protein / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Gene Expression Profiling
  • HeLa Cells
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism
  • Histones / metabolism*
  • Humans
  • Lysine / genetics
  • Lysine / metabolism*
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • Mutation
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism
  • Phosphorylation
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • Substrate Specificity
  • Threonine / genetics
  • Threonine / metabolism
  • Transplantation, Heterologous

Substances

  • Histones
  • Threonine
  • CREB-Binding Protein
  • Histone Acetyltransferases
  • Proto-Oncogene Proteins c-akt
  • Lysine