SMRTER, a Drosophila Nuclear Receptor Coregulator, Reveals that EcR-Mediated Repression Is Critical for Development

• Published in: Molecular cell Vol. 4; no. 2; pp. 175 - 186
• Main Authors: Tsai, Chih-Cheng, Kao, Hung-Ying, Yao, Tso-Pang, McKeown, Michael, Evans, Ronald M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.1999
• Subjects: Amino Acid Sequence; Animals; Biological Evolution; Cell Line; Chromosome Mapping; Chromosomes - genetics; Chromosomes - ultrastructure; Co-Repressor Proteins; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Drosophila; Drosophila melanogaster - embryology; Drosophila melanogaster - growth & development; Drosophila melanogaster - physiology; Drosophila Proteins; Female; Genetic Variation; Male; Molecular Sequence Data; Nuclear Proteins - chemistry; Nuclear Receptor Co-Repressor 1; Nuclear Receptor Co-Repressor 2; Receptors, Cytoplasmic and Nuclear - chemistry; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - physiology; Receptors, Steroid - physiology; Recombinant Proteins - biosynthesis; Recombinant Proteins - chemistry; Repressor Proteins - chemistry; Sequence Alignment; Sequence Homology, Amino Acid; Transfection; Vertebrates
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(00)80365-2

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.