Short heterodimer partner (SHP) orphan nuclear receptor inhibits the transcriptional activity of aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT)

C. M. Klinge, S. C. Jernigan, K. E. Risinger, J. E. Lee, V. V. Tyulmenkov, K. C. Falkner, R. A. Prough

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

SHP (short heterodimer partner) is an orphan nuclear receptor lacking a DNA binding domain that interacts with nuclear receptors (NR) including thyroid receptor (TR), retinoic acid receptors (RAR and RXR), and estrogen receptors α and β (ERα and ERβ). SHP acts as a negative regulator of these receptors by inhibiting DNA binding and transcriptional activation. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) binds to arylhydrocarbon receptor (AHR), activating the AHR/AHR nuclear translocator (ARNT) heterodimer. We investigated the physical and functional interaction of SHP with AHR/ ARNT. In RL95-2 human endometrial carcinoma cells, SHP inhibited TCDD-stimulated reporter activity from the AHR-responsive CYP1A1 and UGT1A6 gene promoters in a concentration-dependent manner. In GST pulldown assays, ARNT interacted directly with SHP in vitro, but AHR did not interact with GST-SHP. SHP inhibited AHR/ARNT-DNA binding in vitro. These results identify ARNT as a novel SHP target. We speculate a role for SHP in the suppression of agonist-activated AHR/ ARNT activity.

Original languageEnglish (US)
Pages (from-to)64-70
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume390
Issue number1
DOIs
StatePublished - Jun 1 2001

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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