Assembly of the SMRT–histone deacetylase 3 repression complex requires the TCP-1 ring complex
- 1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and Department of Genetics and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA; 2Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104 USA; 3Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
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.
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Footnotes
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↵4 Corresponding author.
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E-MAIL lazar{at}mail.med.upenn.edu; FAX (215) 898-5408.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1037502.
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- Received September 3, 2002.
- Accepted October 21, 2002.
- Cold Spring Harbor Laboratory Press
