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  • Title: SMRTER, a Drosophila nuclear receptor coregulator, reveals that EcR-mediated repression is critical for development.
    Author: Tsai CC, Kao HY, Yao TP, McKeown M, Evans RM.
    Journal: Mol Cell; 1999 Aug; 4(2):175-86. PubMed ID: 10488333.
    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.
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