Function of nuclear co-repressor protein on thyroid hormone response elements is regulated by the receptor A/B domain.
Recently, a family of nuclear co-repressor proteins (TRACs) have been identified that interact with thyroid hormone (TR) and retinoic acid receptors to mediate ligand-independent repression of gene transcription. In this report, we have cloned and characterized a human TRAC, which when expressed as a truncated protein lacking its repressing domains, can abolish endogenous cellular TRAC activity. Use of this inhibitor has uncovered a differential function of TRACs on negative versus positive thyroid hormone response elements and has demonstrated the importance of the TR A/B domain in modulating TRAC function. Thus, isoform-specific functions of the TR may be mediated by their functional interaction with co-repressor proteins.
Thyroid Unit, Department of Medicine, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
A N
AN
Hollenberg
T
T
Monden
J P
JP
Madura
K
K
Lee
F E
FE
Wondisford
D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C539127:NCOR1 protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors