Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex

Genes Dev. 2002 Dec 15;16(24):3130-5. doi: 10.1101/gad.1037502.

Abstract

The acetylation of histone tails is a primary determinant of gene activity. Histone deacetylase 3 (HDAC3) requires the nuclear receptor corepressor SMRT for HDAC enzyme activity. Here we report that HDAC3 interacts with SMRT only after priming by cellular chaperones including the TCP-1 ring complex (TRiC), which is required for proper folding of HDAC3 in an ATP-dependent process. SMRT displaces TRiC from HDAC3, yielding an active HDAC enzyme. The SMRT-HDAC3 repression complex thus joins the VHL-elongin BC tumor suppression complex and the cyclin E-Cdk2 cell cycle regulation complex as critical cellular machines requiring TRiC for proper assembly and function. The strict control of HDAC3 activity underscores the cellular imperative that histone deacetylation occur only in targeted regions of the genome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Baculoviridae / genetics
  • Baculoviridae / metabolism
  • Benzoquinones
  • Cell Nucleus / metabolism
  • Chaperonin Containing TCP-1
  • Chaperonins / genetics
  • Chaperonins / metabolism*
  • DNA-Binding Proteins / physiology*
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Fluorescent Antibody Technique
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Lactams, Macrocyclic
  • Microscopy, Confocal
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Receptor Co-Repressor 1
  • Nuclear Receptor Co-Repressor 2
  • Protein Binding / drug effects
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Quinones / pharmacology
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / physiology*
  • Transcription, Genetic
  • Tumor Cells, Cultured / metabolism

Substances

  • Benzoquinones
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Lactams, Macrocyclic
  • NCOR1 protein, human
  • NCOR2 protein, human
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 1
  • Nuclear Receptor Co-Repressor 2
  • Quinones
  • Recombinant Proteins
  • Repressor Proteins
  • Adenosine Triphosphate
  • Protein-Tyrosine Kinases
  • Histone Deacetylases
  • histone deacetylase 3
  • Chaperonin Containing TCP-1
  • Chaperonins
  • geldanamycin