title: Biological roles and mechanistic actions of co-repressor complexes.
abstract: Transcriptional repression, which plays a crucial role in diverse biological processes, is mediated in part by non-DNA-binding co-repressors. The closely related co-repressor proteins N-CoR and SMRT, although originally identified on the basis of their ability to associate with and confer transcriptional repression through nuclear receptors, have been shown to be recruited to many classes of transcription factor and are in fact components of multiple protein complexes containing histone deacetylase proteins. This association with histone deacetylase activity provides an important component of the mechanism that allows DNA-binding proteins interacting with N-CoR or SMRT to repress transcription of specific target genes. Both N-CoR and SMRT are important targets for cell signaling pathways, which influence their expression levels, subcellular localization and association with other proteins. Recently, the biological importance of these proteins has been revealed by studies of genetically engineered mice and human diseases such as acute promyelocytic leukemia (APL) and resistance to thyroid hormone (RTH).
authors.affiliation: Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 920393-0648, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Jepsen
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000235:genetics; D046911:Macromolecular Substances; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D018382:Thyroid Hormone Resistance Syndrome / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; C539127:NCOR1 protein, human; C539130:NCOR2 protein, human; C539128:Ncor1 protein, mouse; C539131:Ncor2 protein, mouse; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D012097:Repressor Proteins; D014157:Transcription Factors; D006655:Histone Deacetylases