Abstract
The Drosophila ecdysone receptor (EcR)/ultraspiracle (USP) heterodimer is a key regulator in molting and metamorphoric processes, activating and repressing transcription in a sequence-specific manner. Here, we report the isolation of an EcR-interacting protein, SMRTER, which is structurally divergent but functionally similar to the vertebrate nuclear corepressors SMRT and N-CoR. SMRTER mediates repression by interacting with Sin3A, a repressor known to form a complex with the histone deacetylase Rpd3/HDAC. Importantly, we identify an EcR mutant allele that fails to bind SMRTER and is characterized by developmental defects and lethality. Together, these results reveal a novel nuclear receptor cofactor that exhibits evolutionary conservation in the mechanism to achieve repression and demonstrate the essential role of repression in hormone signaling.
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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Animals
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Biological Evolution
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Cell Line
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Chromosome Mapping
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Chromosomes / genetics
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Chromosomes / ultrastructure
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Co-Repressor Proteins
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Drosophila Proteins*
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Drosophila melanogaster / embryology
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Drosophila melanogaster / growth & development
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Drosophila melanogaster / physiology*
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Female
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Genetic Variation
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Male
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Molecular Sequence Data
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Nuclear Proteins / chemistry
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Nuclear Receptor Co-Repressor 1
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Nuclear Receptor Co-Repressor 2
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / physiology*
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Receptors, Steroid / physiology*
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Repressor Proteins / chemistry
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Sequence Alignment
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Sequence Homology, Amino Acid
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Transfection
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Vertebrates
Substances
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Co-Repressor Proteins
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DNA-Binding Proteins
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Drosophila Proteins
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Nuclear Proteins
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Nuclear Receptor Co-Repressor 1
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Nuclear Receptor Co-Repressor 2
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Recombinant Proteins
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Repressor Proteins
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Smr protein, Drosophila
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ecdysone receptor