Role of GAC63 in transcriptional activation mediated by the aryl hydrocarbon receptor

Yong Heng Chen, Timothy V. Beischlag, Hoon Kim Jeong, Gary H. Perdew, Michael R. Stallcup

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The aryl hydrocarbon receptor (AHR), amember of the basic helix-loop-helix/Per-Arnt-Sim (bHLH-PAS) gene family, binds a variety of polycyclic aromatic hydrocarbons and mediates their toxic effects. GAC63 has been shown to act as a coactivator in nuclear receptor-mediated gene transcription. In this report, we demonstrate that GAC63 interacts with AHR through its bHLH-PAS domain. Overexpression of GAC63 greatly enhanced AHR-regulated reporter gene activity in a ligand-dependent manner in transient transfection assays. Upon ligand treatment, endogenous GAC63 was recruited to the xenobiotic response element of the mouse CYP1A1 gene, an AHR-responsive gene. Reduction of the endogenous GAC63 level by small interfering RNA inhibited transcriptional activation by AHR. These findings reveal a new function of GAC63 in AHR-mediated gene transcription.

Original languageEnglish (US)
Pages (from-to)12242-12247
Number of pages6
JournalJournal of Biological Chemistry
Volume281
Issue number18
DOIs
StatePublished - May 5 2006

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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