The N-CoR-HDAC3 Nuclear Receptor Corepressor Complex Inhibits the JNK Pathway through the Integral Subunit GPS2
Open accessAbstract
The corepressors N-CoR and SMRT partner with histone deacetylases (HDACs) in diverse repression pathways. We report here that GPS2, a protein involved in intracellular signaling, is an integral subunit of the N-CoR-HDAC3 complex. We have determined structural motifs that direct the formation of a highly stable and active deacetylase complex. GPS2 and TBL1, another component of the N-CoR-HDAC3 complex, interact cooperatively with repression domain 1 of N-CoR to form a heterotrimeric structure and are indirectly linked to HDAC3 via an extended N-CoR SANT domain that also activates latent HDAC3 activity. More importantly, we show here that the N-CoR-HDAC3 complex inhibits JNK activation through the associated GPS2 subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP-1 function.
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The DAD both recruits and activates HDAC3.
“The DAD both recruits and activates HDAC310-12.”
From Structure of Hdac3 Bound to Co-Repressor and Inositol Tetraphosphate (2012) · cites this paper as [10]
HDACs 1, 2 and 3 require association with large multisubunit corepressor complexes for maximal activity.
“HDACs 1, 2 and 3 require association with large multisubunit corepressor complexes for maximal activity7-12.”
From Structure of Hdac3 Bound to Co-Repressor and Inositol Tetraphosphate (2012) · cites this paper as [10]
HDAC3 appears to be uniquely recruited to the SMRT/NCoR complex, where it interacts with a conserved deacetylase-activation-domain (DAD) within SMRT or NCoR.
“In contrast, HDAC3 appears to be uniquely recruited to the SMRT/NCoR complex where it interacts with a conserved deacetylase-activation-domain (DAD) within SMRT or NCoR8,10,12,24,25,26.”
From Structure of Hdac3 Bound to Co-Repressor and Inositol Tetraphosphate (2012) · cites this paper as [10]
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- Authors
- Zhang, J., Kalkum, M., Chait, B. T., & Roeder, R. G.
- Affiliations
- Rockefeller University (US)
- Corresponding author
- Roeder, Robert G
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 9
- Issue
- 3
- Pages
- 611-623
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2115446838
- Cited by
- 414
- References
- 32
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 15 · 2023: 11 · 2022: 12 · 2021: 10 · 2020: 21 · 2019: 9 · 2018: 15 · 2017: 22 · 2016: 14 · 2015: 16 · 2014: 17 · 2013: 16 · 2012: 19
- FWCI
- 9.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- 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 › Epigenetics and DNA Methylation
- Keywords
- NCoR, SMRT, HDAC3, GPS2, TBL1, histone deacetylase complex, JNK signaling, AP-1, SANT domain, heterotrimeric complex, protein complex structure
- MeSH terms
- Histone Deacetylase 3, Amino Acid Sequence, HeLa Cells, Histone Deacetylases, Humans, Molecular Sequence Data, Nuclear Proteins, Recombinant Fusion Proteins, Repressor Proteins, Protein Structure, Tertiary, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Protein Subunits, Macromolecular Substances, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Nuclear Receptor Co-Repressor 1
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