Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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HeLa Cells
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Histone Deacetylases / isolation & purification
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Histone Deacetylases / metabolism*
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Humans
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Intracellular Signaling Peptides and Proteins
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Signaling System / physiology*
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Macromolecular Substances
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Mitogen-Activated Protein Kinases / metabolism*
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Molecular Sequence Data
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Nuclear Proteins / isolation & purification
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Nuclear Proteins / metabolism*
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Nuclear Receptor Co-Repressor 1
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Protein Structure, Tertiary
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Protein Subunits
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Recombinant Fusion Proteins
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Repressor Proteins / isolation & purification
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Repressor Proteins / metabolism*
Substances
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GPS2 protein, human
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Intracellular Signaling Peptides and Proteins
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Macromolecular Substances
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NCOR1 protein, human
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Nuclear Proteins
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Nuclear Receptor Co-Repressor 1
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Protein Subunits
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Recombinant Fusion Proteins
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Repressor Proteins
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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Histone Deacetylases
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histone deacetylase 3