Role of GAC63 in transcriptional activation mediated by the aryl hydrocarbon receptor.
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.
Chen
Yong-Heng
YH
Department of Pathology, University of Southern California, Los Angeles, California 90089, USA.
Beischlag
Timothy V
TV
Kim
Jeong Hoon
JH
Perdew
Gary H
GH
Stallcup
Michael R
MR
D000818:Animals; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D008024:Ligands; D051379:Mice; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015262:Xenobiotics
C503320:GAC63 protein, mouse; D008024:Ligands; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D015262:Xenobiotics; D019363:Cytochrome P-450 CYP1A1