AhR nuclear translocator

Klinge, C. M., Bowers, J.L., Kulakosky, P. C., Kamboj, K.K. and Swanson, H.I. (1999) The aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT) heterodimer interacts with naturally occurring estrogen response elements. 

Figure 5.33 Mechanism of the receptor-mediated induction of CYP1A1 by a polycyclic hydrocarbon such as TCDD. The inducer-receptor (AhR) complex enters the nucleus, binds with ARNT, and the complex binds to the CYP1A1 gene in the DNA. This induces the production of CYP1A1 mRNA, which leads to the production of CYP1A1 protein and functional enzyme. Abbreviations AIP, AhR interacting protein AhR, aryl hydrocarbon receptor HSP, heat shock protein 90 ARNT, AhR nuclear translocator E.R., endoplasmic reticulum.

Abbreviations used in text AA, arachidonic acid AhR, aryl hydrocarbon receptor Amt, AhR nuclear translocator BR, bilirubin BV, biliverdin CYP1A1, cytochrome P4501A1 DRE, dioxin responsive element FICZ, 6-formylindolo(3,2b)carbazole HAH, halogenated aromatic hydrocarbon I3C, indole 3-carbinol ICZ, indolo-(3,2,-b)-carbazole PAH, polycyclic aromatic hydrocarbon RAR, retinoic acid receptor TCDD, 2,3,7,8-tetrachlorodi benzo-/>-dioxin Trp, tryptophan UGT 01, UDP-glucuronosy 1 transferase 01... 

The AhR is a well-researched receptor in a mammalian dioxin-dependent inducible expression system (Figrue 1) [5], Dioxins that are transferred into mammalian cells specihcaUy bind to the AhR complex, which then is transported into the nucleus, where it forms a heterodimer with an AhR nuclear translocator (Arnt). The heterodimer binds to a xenobiotic responsive element (XRE) upstream of the gene for a drug-metabolizing enzyme (GYPlAl). This binding induces the production of CYPlAl mRNA and thus the production of the GYPlAl enzyme, which metabolizes some dioxins. 

Arnt = AhR nuclear translocator XRE = xenobiotic responsive element Hsp90 = heat shock protein 90 T = terminator R = substrate. 

Several ClPAHs have been determined to be AhR-active. AhR-mediated toxicity (Fig. 5) is activated by all embryotoxic HAH and PAH congeners [212, 219, 220] toward nuclear translocation, where the AhR heterodimerizes with the AhR nuclear translocator (ARNT). The resulting ligand-AhR-ARNT complex further combines with various coactivators and promotes their expression through interacting in the... 

Fig. 5 Generic mechanism of AhR-mediated toxicity AhR mediates signal transduction by dioxin-like ligands, which form a transcription factor complex with an aryl hydrocarbon nuclear translocator protein (ARNT). This heterodimer recognizes specific DNA sequences, namely dioxin responsive elements (DREs), and leads to induction of several genes forming the so-called Ah gene battery. In this process, the elevated levels of the protein products are assumed to be involved in the toxic action of AhR ligands. AIP AhR inhibitory protein, hsp90 90-kDa heat shock protein, ARNT AhR nuclear translocator, XRE xenobiotic response element, CYPIA eyto-chrome P450 lA gene/protein (adapted from [211, 212])...

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