Abstract
Transcriptional silencing mediated by nuclear receptors is important in development, differentiation and oncogenesis. The mechanism underlying this effect is unknown but is one key to understanding the molecular basis of hormone action. Here we identify a receptor-interacting factor, SMRT, as a silencing mediator (co-repressor) for retinoid and thyroid-hormone receptors. SMRT is a previously undiscovered protein whose association with receptors both in solution and bound to DNA-response elements is destabilized by ligand. The interaction with mutant receptors correlates with their transcriptional silencing activities. In vivo, SMRT functions as a potent co-repressor, and a GAL4 DNA-binding domain fusion of SMRT behaves as a frank repressor of a GAL4-dependent reporter. Together, our results identify a new class of cofactors which may be important mediators of hormone action.
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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Cell Line
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DNA / metabolism
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DNA-Binding Proteins / metabolism*
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Fungal Proteins / genetics
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Gene Expression Regulation*
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Genes, Reporter
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Humans
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Ligands
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Molecular Sequence Data
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Mutagenesis
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Nuclear Receptor Co-Repressor 2
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Oncogene Proteins v-erbA / genetics
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Receptors, Retinoic Acid / metabolism*
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Receptors, Thyroid Hormone / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / metabolism*
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Saccharomyces cerevisiae
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Saccharomyces cerevisiae Proteins*
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Transcription Factors*
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Transcription, Genetic*
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Transfection
Substances
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DNA-Binding Proteins
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Fungal Proteins
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GAL4 protein, S cerevisiae
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Ligands
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NCOR2 protein, human
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Nuclear Receptor Co-Repressor 2
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Oncogene Proteins v-erbA
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Recombinant Fusion Proteins
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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DNA