title: SMRTε, a corepressor variant, interacts with a restricted subset of nuclear receptors, including the retinoic acid receptors α and β.
abstract: The SMRT and NCoR corepressors bind to, and mediate transcriptional repression by, many nuclear receptors. Both SMRT and NCoR are expressed by alternative mRNA splicing, generating a series of structurally and functionally distinct corepressor "variants". We report that a splice variant of SMRT, SMRTε, recognizes a restricted subset of nuclear receptors. Unlike the other corepressor variants characterized, SMRTε possesses only a single receptor interaction domain (RID) and exhibits an unusual specificity for a subset of nuclear receptors that includes the retinoic acid receptors (RARs). The ability of the single RID in SMRTε to efficiently interact with RARs appears to be enhanced by a recently recognized β-strand/β-strand interaction between corepressor and receptor. We suggest that alternative mRNA splicing of corepressors can restrict their function to specific nuclear receptor partnerships, and we propose that this may serve to customize the transcriptional repression properties of different cell types for different biological purposes.
authors.affiliation: Department of Microbiology, One Shields Avenues, University of California at Davis, CA 95616, USA.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Mengeling
authors.forename: Michael L
authors.initials: ML
authors.lastname: Goodson
authors.forename: William
authors.initials: W
authors.lastname: Bourguet
authors.forename: Martin L
authors.initials: ML
authors.lastname: Privalsky
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D000071518:Liver X Receptors; D051379:Mice; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism; D056985:Nuclear Receptor Co-Repressor 2 / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma
chemical_list: D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D057093:Orphan Nuclear Receptors; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C000607072:Rara protein, mouse; C082925:retinoic acid receptor beta