SMRTER, a Drosophila nuclear receptor coregulator, reveals that EcR-mediated repression is critical for development.
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.
Tsai
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CC
Gene Expression Lab, Salk Institute, La Jolla, California 92037, USA.
Kao
H Y
HY
Yao
T P
TP
McKeown
M
M
Evans
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002460:Cell Line; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics / Q000648:ultrastructure; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011987:Receptors, Steroid / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D012097:Repressor Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014714:Vertebrates
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011994:Recombinant Proteins; D012097:Repressor Proteins; C121508:Smr protein, Drosophila; C055469:ecdysone receptor