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    J Biol Chem. 2006 May 5;281(18):12242-7. Epub 2006 Mar 2.

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

    Chen YH, Beischlag TV, Kim JH, Perdew GH, Stallcup MR.

    Source

    Department of Pathology, University of Southern California, Los Angeles, California 90089, USA.

    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.

    PMID:
    16513642
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC1770942
    Free PMC Article

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