Aryl hydrocarbon nuclear translocator

Tanguay, R.L., E. Andreasen, W. Heideman and R.E. Peterson. Identification and expression of alternatively spliced aryl hydrocarbon nuclear translocator 2 (ARNT2) cDNAs from zebrafish with distinct functions. Biochim. Biophys. Acta 1494 117—128, 2000. 

Pollenz, R.S., N.A. Davarinos, and T.P. Shearer (1999). Analysis of aryl hydrocarbon receptor-mediated signaling during physiological hypoxia reveals lack of competition for the aryl hydrocarbon nuclear translocator transcription factor. Mol. Pharmacol. 56, 1127-1137. 

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])...

HIF3a is not well known (51). HIFl, or ARNT, the aryl-hydrocarbon nuclear translocator, belongs to the class I of bHLH-PAS proteins and was first described as binding to the aryl hydrocarbon receptor (AHR), which is also a member of class II of bHLH-PAS proteins (46). 

Marcus, R., Holsapple, M., and Kaminski, N., Lipopolysaccharide activation of murine splenocytes and splenic B cells increased the expression of aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator, J. Pharmacol. Exper. Therap.. 287, 1113, 1998. 

Camacho, I., et. al., Treatment of mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin leads to aryl hydrocarbon receptor-dependent nuclear translocation of NF-kappa B and expression of Fas ligand in thymic stromal cells and consequent T cell apoptosis, J. Immunol., 175, 90, 2005. 

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. 

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the expression of cytochrome P450 lAl, the aryl hydrocarbon receptor, and the aryl hydrocarbon receptor nuclear translocator in rat brain and pituitary. Toxicol Appl Pharmacol 169 159-167. 

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.

Choi H, Chun YS, Kim SW, Kim MS, Park JW. 2006. Curcumin inhibits hypoxia-inducible factor-1 by degrading aryl hydrocarbon receptor nuclear translocator A mechanism of tumor growth inhibition. Mol Pharmacol 70 1664-1671. 

Abbott BD, Probst MR. 1995. Developmental expression of two members of a new class of transcription factors II. Expression of aryl hydrocarbon receptor nuclear translocator in the C57BL/6N mouse embryo. Develop Dynam 204 144-155... 

Hirose K, Morita M, Ema M, et al. 1996. cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS factor (Amt2) with close sequence similarity to the aryl hydrocarbon receptor nuclear translocator (Amt). Mol Cell Biol 16 1706-1713. 

Pollenz RS, Sattler CA, Poland A. 1994. The aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator protein show distinct subcellular localizations in Hepa lclc7 cells by immunofluorescence microscopy. Mol Pharmacol 45 428-438. 

Scheel J, Hussong R, Schrenk D, Schmitz HJ. Variability of the human aryl hydrocarbon receptor nuclear translocator (ARNT) gene. J Hum Genet 2002 47 217-224. 

Figure 32.6. Model of AhR-mediated mechanism of action of TCDD and related HAHs. TCDD binds to the AhR in the cytoplasm. This complex interacts with another cytosolic protein (ARNT) and is translocated into the nucleus where it binds to specific DNA enhancer sequences upstream of TCDD responsive genes. Exactly which genes are important in the resulting immune suppression is unclear. Abbreviations AhR, aryl hydrocarbon receptor ARNT, AhR nuclear transporter DRE, dioxin-responsive elements.

Both a and P subunits of HIF are basic helix-loop-helix PAS proteins (bHLH-PAS) (6, 7), as observed in other transcription-factor proteins (Fig. 2). The short, basic region of bHLH-PAS proteins is directly responsible for DNA binding, and the adjacent helix-loop-helix domain allows dimerization of the two HIF subunits after translocation of HIF-a to the nucleus. The PAS domain [PAS-A/PAS-B/PAC PAS PER (periodic circadian protein), aryl hydrocarbon receptor nuclear translocator (ARNT), single-minded protein (SIM) (7) PAC motif C-terminal to PAS motifs) is involved in more specific interactions between the two subunits (for review see Reference 8). It is proposed that the specific interaction between the HIF-a and HIF-P subunits promotes folding and dimerization of the bHLH region that enables subsequent DNA binding (8). HIF-a is a Class 1 bHLH-PAS protein, which means that it can homodimer-ize and heterodimerize HIF-3 (also known as ARNT, which is... 

Hur E, Kim HH, Choi SM, Kim JH, Yim S, Kwon HJ, Choi Y, Kim DK, Lee MO, Park H. Reduction of hypoxia-induced transcription through the repression of hypoxia-inducible factor-lalpha/aryl hydrocarbon receptor nuclear translocator DNA binding by the 90-kDa heat-shock protein inhibitor radicicol. Mol. Pharmacol. 2002 62 975-982. 

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... 

Hord NG, Perdew GH. 1994. Physio-chemical and immunochemical analysis of aryl hydrocarbon receptor nuclear translocator characterization oftwo monoclonal antibodies to the aryl hydrocarbon receptor nuclear translocator. Molec. Pharmacol. 46 618-24... 

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