Direct interaction of Ca2+/calmodulin inhibits histone deacetylase 5 repressor core binding to myocyte enhancer factor 2

J Biol Chem. 2003 May 16;278(20):17625-35. doi: 10.1074/jbc.M301646200. Epub 2003 Mar 6.

Abstract

Myocyte enhancer factor 2 (MEF2) proteins play a pivotal role in the differentiation of cardiac and skeletal muscle cells. MEF2 factors are regulated by histone deacetylase enzymes such as histone deacetylase 5 (HDAC5). HDAC5 in turn is responsive to Ca(2+) signaling mediated by the intracellular calcium sensor calmodulin. Here a combination of proteolytic fragmentation, matrix-assisted laser desorption ionization mass spectrometry, Edman degradation, circular dichroism, gel filtration, and surface plasmon resonance studies is utilized to define and characterize a stable core domain of HDAC5 and to examine its interactions with MEF2a and calmodulin. Results from real time binding experiments provide evidence for direct interaction of Ca(2+)/calmodulin with HDAC5 inhibiting MEF2a association with this enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Calcium / metabolism*
  • Calmodulin / chemistry
  • Calmodulin / metabolism*
  • Cells, Cultured
  • Chromatography, Gel
  • Circular Dichroism
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / metabolism*
  • Egtazic Acid / pharmacology
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / metabolism*
  • Humans
  • Kinetics
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Myogenic Regulatory Factors
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Surface Plasmon Resonance
  • Time Factors
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism*
  • Trypsin / pharmacology

Substances

  • Calmodulin
  • DNA-Binding Proteins
  • Histone Deacetylase Inhibitors
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • MEF2A protein, human
  • Myogenic Regulatory Factors
  • Transcription Factors
  • Egtazic Acid
  • Trypsin
  • HDAC5 protein, human
  • Histone Deacetylases
  • Calcium