The nuclear corepressors recognize distinct nuclear receptor complexes

R. N. Cohen, A. Putney, Fredric Wondisford, A. N. Hollenberg

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

The thyroid hormone receptor (TR) and retinoic acid receptor (RAR) isoforms have the capacity to silence gene expression in the absence of their ligands on target response elements. This active repression is mediated by the ability of the corepressors, nuclear receptor corepressor (NCoR) and silencing mediator of retinoid and thyroid hormone receptors (SMRT), to recruit a complex containing histone deacetylase activity. Interestingly, NCoR and SMRT share significant differences in the their two nuclear receptor-interacting domains (IDs), suggesting that they may recruit receptors with different affinities. In addition, the role of the receptor complex bound to a response element has not been fully evaluated in its ability to recruit separate corepressors. We demonstrate in this report that the proximal ID in NCoR and SMRT, which share only 23% homology, allows preferential recognition of nuclear receptors, such that TR prefers to recruit NCoR, and RAR prefers to recruit SMRT, to DNA response elements. However, mutations in the TR found in the syndromes of resistance to thyroid hormone can change the corepressor recruited by changing the complex (homodimer or heterodimer) formed on the TRE. These results demonstrate that the corepressor complex recruited can be both nuclear receptor- and receptor complex-specific.

Original languageEnglish (US)
Pages (from-to)900-914
Number of pages15
JournalMolecular Endocrinology
Volume14
Issue number6
DOIs
StatePublished - Jan 1 2000

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Co-Repressor Proteins
Cytoplasmic and Nuclear Receptors
Thyroid Hormone Receptors
Response Elements
Retinoic Acid Receptors
Thyroid Hormone Resistance Syndrome
Histone Deacetylases
Retinoids
Protein Isoforms
Ligands
Gene Expression
Mutation
DNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

Cite this

Cohen, R. N. ; Putney, A. ; Wondisford, Fredric ; Hollenberg, A. N. / The nuclear corepressors recognize distinct nuclear receptor complexes. In: Molecular Endocrinology. 2000 ; Vol. 14, No. 6. pp. 900-914.
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The nuclear corepressors recognize distinct nuclear receptor complexes. / Cohen, R. N.; Putney, A.; Wondisford, Fredric; Hollenberg, A. N.

In: Molecular Endocrinology, Vol. 14, No. 6, 01.01.2000, p. 900-914.

Research output: Contribution to journalArticle

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