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

The Journal of Biological Chemistry
Yong-Heng ChenMichael R Stallcup

Abstract

The aryl hydrocarbon receptor (AHR), a member 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.

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Citations

Mar 9, 2007·Nucleic Acids Research·Yong-Heng ChenMichael R Stallcup
Oct 10, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Robert T TaylorOliver Hankinson
Aug 19, 2010·The Journal of Pharmacology and Experimental Therapeutics·Gary H PerdewTimothy V Beischlag
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Dec 1, 2007·Toxicology and Applied Pharmacology·Shu ZhangStephen Safe
Jan 30, 2010·Journal of Cellular Physiology·Carrie L Partch, Kevin H Gardner
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Dec 20, 2019·Cancer Science·Ai Hironaka-MitsuhashiTakahiro Ochiya
Jan 2, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Guiying ZhangXiuwu Zhang
Jan 1, 2021·Gut Microbes·Fangcong Dong, Gary H Perdew
Apr 8, 2020·Chemical Research in Toxicology·Mele N AvillaChristopher A Bradfield
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