The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2.
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.
Mesh Terms:
Amino Acid Sequence, Hela Cells, Histone Deacetylases, Humans, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Macromolecular Substances, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Nuclear Proteins, Nuclear Receptor Co-Repressor 1, Protein Structure, Tertiary, Protein Subunits, Recombinant Fusion Proteins, Repressor Proteins
Amino Acid Sequence, Hela Cells, Histone Deacetylases, Humans, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Macromolecular Substances, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Nuclear Proteins, Nuclear Receptor Co-Repressor 1, Protein Structure, Tertiary, Protein Subunits, Recombinant Fusion Proteins, Repressor Proteins
Mol. Cell
Date: Mar. 01, 2002
PubMed ID: 11931768
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