Assembly of the SMRT–histone deacetylase 3 repression complex requires the TCP-1 ring complex
Open accessAbstract
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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HDAC3 and SMRT-DAD do not form a complex when expressed in bacterial cells.
“It has been proposed that the assembly of the HDAC3 and SMRT-DAD requires a chaperone complex, since when these proteins are expressed in bacteria they do not form a complex30.”
From Structure of Hdac3 Bound to Co-Repressor and Inositol Tetraphosphate (2012) · cites this paper as [30]
The Conclusion (page not provided) proposes that TRiC primes HDAC3 to interact with SMRT, supporting the chaperone-complex part of the citing sentence. It discusses HDAC3 purified from insect cells, but does not report whether HDAC3 and SMRT-DAD form a complex when expressed in bacteria. (LLM, conf=0.83)
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Structure of Hdac3 Bound to Co-Repressor and Inositol Tetraphosphate
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- Authors
- Guenther, M. G., Yu, J., Kao, G. D., Yen, T. J., & Lazar, M. A.
- Affiliations
- Fox Chase Cancer Center (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2002-12-15
- Volume
- 16
- Issue
- 24
- Pages
- 3130-3135
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC187500
- OpenAlex
- W1964623135
- Cited by
- 138
- References
- 31
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 9 · 2020: 2 · 2019: 6 · 2018: 6 · 2017: 2 · 2016: 4 · 2015: 9 · 2014: 7 · 2013: 8 · 2012: 6
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (CA-06927, DK43806)
- National Cancer Institute (P30CA006927, CA06927)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK43806, R01DK045586, DK 45586, R37DK043806, R01DK043806)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- SMRT, HDAC3, TRiC chaperonin, protein folding, nuclear receptor corepressor, histone deacetylation, gene repression, cyclin E-Cdk2 complex, protein complex formation, ATP-dependent folding
- MeSH terms
- Histone Deacetylase 3, Adenosine Triphosphate, Cell Nucleus, DNA-Binding Proteins, Enzyme Activation, Enzyme Inhibitors, Fluorescent Antibody Technique, Histone Deacetylases, Humans, Nuclear Proteins, Protein Binding, Protein-Tyrosine Kinases, Quinones, Recombinant Proteins, Repressor Proteins, Transcription, Genetic, Tumor Cells, Cultured, Benzoquinones, Baculoviridae, Microscopy, Confocal, Chaperonins, Lactams, Macrocyclic, Chaperonin Containing TCP-1, Nuclear Receptor Co-Repressor 1, Nuclear Receptor Co-Repressor 2
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