title: Transcriptional repression by nuclear receptors: mechanisms and role in disease.
abstract: Co-repressor proteins mediate transcriptional repression by nuclear receptors in the absence of ligand. The identification of a co-repressor-receptor interaction motif, and the finding that co-repressors and co-activators compete for the same site on the receptor, suggests a simple mechanism for the switch from repression to activation upon ligand binding. Defects in this mechanism result in dominant-negative receptors that repress transcription. Such receptors have been implicated in several clinically important diseases, including thyroid hormone resistance and diabetes mellitus.
authors.affiliation: MRC-Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, U.K. and Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, U.K.
authors.forename: J D
authors.initials: JD
authors.lastname: Love
authors.forename: J T
authors.initials: JT
authors.lastname: Gooch
authors.forename: L
authors.initials: L
authors.lastname: Nagy
authors.forename: V K
authors.initials: VK
authors.lastname: Chatterjee
authors.forename: J W
authors.initials: JW
authors.lastname: Schwabe
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018382:Thyroid Hormone Resistance Syndrome / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D008024:Ligands