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

Matthew G. Guenther, Jiujiu Yu, Gary D. Kao, Tim J. Yen, Mitchell A. Lazar

Research output: Contribution to journalArticle

97 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3130-3135
Number of pages6
JournalGenes and Development
Volume16
Issue number24
DOIs
StatePublished - Dec 15 2002

Fingerprint

Histones
Co-Repressor Proteins
Cyclin E
Enzymes
Acetylation
histone deacetylase 3
Cell Cycle
Adenosine Triphosphate
Genome
Genes
Neoplasms
elongin

Keywords

  • Corepressor
  • HDAC3
  • Histone deacetylase
  • N-CoR
  • SMRT
  • TRiC

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex. / Guenther, Matthew G.; Yu, Jiujiu; Kao, Gary D.; Yen, Tim J.; Lazar, Mitchell A.

In: Genes and Development, Vol. 16, No. 24, 15.12.2002, p. 3130-3135.

Research output: Contribution to journalArticle

Guenther, Matthew G. ; Yu, Jiujiu ; Kao, Gary D. ; Yen, Tim J. ; Lazar, Mitchell A. / Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex. In: Genes and Development. 2002 ; Vol. 16, No. 24. pp. 3130-3135.
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