A nuclear hormone receptor-associated protein that inhibits transactivation by the thyroid hormone and retinoic acid receptors

Thomas P. Burris, Zafar Nawaz, Ming Jer Tsai, Bert W. O'Malley

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Nuclear hormone receptors are transcription factors that require multiple protein-protein interactions to regulate the expression of their target genes. Using the yeast two-hybrid system, we identified a protein, thyroid hormone receptor uncoupling protein (TRUP), that specifically interacts with a region of the human thyroid hormone receptor (TR) consisting of the hinge region and the N-terminal portion of the ligand binding domain in a hormone- independent manner. Interestingly, TRUP inhibits transactivation by TR and the retinoic acid receptor but has no effect on the estrogen receptor or the retinoid X receptor in mammalian cells. We also demonstrate that TRUP exerts its action on TR and retinoic acid receptor by interfering with their abilities to interact with their DNA. TRUP represents a type of regulatory protein that modulates the transcriptional activity of a subclass of the nuclear hormone receptor superfamily by preventing interaction with their genomic response elements.

Original languageEnglish (US)
Pages (from-to)9525-9529
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number21
DOIs
StatePublished - Oct 10 1995
Externally publishedYes

Keywords

  • transcription/steroid receptor/two-hybrid system

ASJC Scopus subject areas

  • Genetics
  • General

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