The dioxin (aryl hydrocarbon) receptor as a model for adaptive responses of bHLH/PAS transcription factors

Abstract 

This review examines the common theme of adaptive responses of bHLH/PAS proteins, using the dioxin receptor as a prototype. The bHLH/PAS family of transcriptional regulators are a group of key developmental and environmental stress sensing proteins. They employ a variety of post-translational control mechanisms to regulate their transcriptional output. Amongst this family, the dioxin receptor is best known for its ability to elicit toxic responses to dioxin and dioxin like chemicals even though it mediates more benign adaptive responses to non-toxic xenobiotics. We discuss what is known about dioxin receptor physiology, both adaptive and inherent, along with its molecular regulation and put this into the context of the wider bHLH/PAS family. We also raise the issue of its toxic responses, in particular the idea that it is the dysregulation of its poorly characterised housekeeping functions that leads to these outcomes.

Keywords: Dioxin receptor, bHLH/PAS, HIF, NXF, ARNT, hsp90, AIP/Ara9/XAP2

Abbreviations: bHLH, basic helix-loop-helix, PAS, PER ARNT Sim, DNA, deoxyribonucleic acid, DR, dioxin receptor, AhR, aryl hydrocarbon receptor, HIF, hypoxia inducible factor, ARNT, aryl hydrocarbon receptor nuclear translocator, HLF, HIF like factor, EPAS, endothelial PAS, PHD, prolyl hydroxylase, VHL, Von-Hippel Lindau, IPAS, inhibitory PAS, PER, period, BMAL, brain and muscle ARNT like protein, NXF, neuronal transcription factor, TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin, NLS, nuclear localisation sequence, NES, nuclear export sequence, hsp90, heat shock protein 90, CoCoA, coiled-coil co-activator, GAC63, GRIP1-associated co-activator 63, CRM-1, chromosome region maintenance protein 1, XRE, xenobiotic response element, ER, estrogen receptor, PKC, protein kinase C, PMA, phorbol 12-myristate 13-acetate, AhRR, AhR repressor, XAP2, hepatitis virus B X associated protein 2

• 1 http://www.med.monash.edu.au/pharmacology/research/ddb.html
• 2 http://www.adelaide.edu.au/mbs/research/whit/