Transcriptional repression by nuclear receptors: mechanisms and role in disease.

J D Love, J T Gooch, L Nagy, V K Chatterjee, J W Schwabe

Journal: Biochemical Society transactions 2001;28(4):390-6

PMID: 10961926

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.

Address: 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.

MeSH Terms: Amino Acid Sequence, Binding Sites, Cell Nucleus, Diabetes Mellitus, Gene Expression Regulation, Humans, Leukemia, Erythroblastic, Acute, Leukemia, Promyelocytic, Acute, Ligands, Models, Biological, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Tertiary, Thyroid Hormone Resistance Syndrome, Transcription, Genetic