Identification of a novel mechanism of regulation of Ah (dioxin) receptor function.
Ah receptor (AhR) is a ligand-activated transcription factor that mediates pleiotropic effects of environmental pollutants such as 2,3, 7,8-tetrachlorodibenzo-p-dioxin on host animals. In addition to induction of drug-metabolizing enzymes, the liganded AhR complex was found to activate gene expression of a factor designated AhR repressor (AhRR), which inhibits AhR function by competing with AhR for dimerizing with Arnt and binding to the XRE sequence. Thus, AhR and AhRR form a regulatory circuit in the xenobiotic signal transduction pathway and provide a novel mechanism of regulation of AhR function that may determine tissue-specific sensitivity to environmental pollutants.
Mimura
J
J
Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan.
Ema
M
M
Sogawa
K
K
Fujii-Kuriyama
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D019281:Dimerization; D005786:Gene Expression Regulation / Q000235:genetics*; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C117300:Ahrr protein, mouse; C497397:Arnt protein, mouse