Aromatic hydrocarbon nuclear translocator as a common component for the hypoxia- and dioxin-induced gene expression.
Aromatic hydrocarbon nuclear translocator (Arnt) is an ubiquitously expressed protein that contains basic helix-loop-helix (bHLH) and Per-AhR-Arnt-Sim (PAS) motifs. Other bHLH-PAS proteins, hypoxia-inducible factor-1alpha (HIF-1alpha) and aromatic hydrocarbon receptor (AhR) mediate hypoxia- and dioxin-signal pathway, respectively. Arnt has been identified as a heterodimerization partner for AhR. AhR/Arnt heterodimer binds the regulatory region of xenobiotic-induced genes and activates their transcription. Here, in vivo results provide evidence that Arnt is involved in not only xenobiotic- but also hypoxia-induced transcriptional activation. In hypoxic condition, Arnt dimerizes with HIF-1alpha to make HIF-1alpha/Arnt heterodimer which is able to bind hypoxia-responsive DNA elements. The HIF-1alpha/Arnt heterodimer functions as a transactivator for hypoxia-inducible genes. Given that the expression of Arnt is limited, HIF-1alpha may compete with AhR for recruiting Arnt as a heteromeric partner. Consistent with this idea, the results indicate that the hypoxic activation of HIF-1alpha reduces dioxin-induced AhR's function on the dioxin-responsive reporter gene and the endogenous gene.
Park
H
H
Department of Life Science, University of Seoul, Korea. hspark@uoscc.uos.ac.kr
D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004147:Dioxins / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins / Q000378:metabolism; D010735:Phosphoglycerate Kinase / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011485:Protein Binding; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D004147:Dioxins; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D003035:Cobalt; D004247:DNA; D019363:Cytochrome P-450 CYP1A1; D010735:Phosphoglycerate Kinase; C018021:cobaltous chloride; D004121:Dimethyl Sulfoxide