An introduction to the molecular basics of aryl hydrocarbon receptor biology.
Depending on their chemical structure and properties, environmental chemicals and other xenobiotics that enter the cell can affect cellular function by either nonselective binding to cellular macromolecules or by interference with cellular receptors, which would initiate a more defined cell biological response. One of these intracellular chemosensor molecules is the aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family that is known to mediate the biochemical and toxic effects of dioxins, polyaromatic hydrocarbons and related compounds. Numerous investigations have revealed that the AhR is not only a master regulator of drug metabolism activated by anthropogenic chemicals, but is also triggered by natural and endogenous ligands and can influence cell biological endpoints such as growth and differentiation. Cutting-edge research has identified new intriguing functions of the AhR, such as during proteasomal degradation of steroid hormone receptors, the cellular UVB stress response and the differentiation of certain T-cell subsets. In this review we provide both a survey of the fundamental basics of AhR biology and an insight into new functional aspects of AhR signaling to further stimulate research on this intriguing transcription factor at the interface between toxicology, cell biology and immunology.
Abel
Josef
J
Institut für Umweltmedizinische Forschung (IUF) an der Heinrich-Heine-Universität Düsseldorf gGmbH, Auf'm Hennekamp 50, Düsseldorf, Germany.
Haarmann-Stemmann
Thomas
T
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D017173:Caenorhabditis elegans; D002454:Cell Differentiation / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004147:Dioxins / Q000494:pharmacology; D004331:Drosophila melanogaster; D004785:Environmental Pollutants / Q000633:toxicity; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000494:pharmacology; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism; D054875:Ubiquitination; D014466:Ultraviolet Rays; D015262:Xenobiotics / Q000378:metabolism / Q000494:pharmacology; D000099162:Endothelial PAS Domain-Containing Protein 1
D000470:Alkaloids; D001189:Aryl Hydrocarbon Hydroxylases; D051792:Basic Helix-Loop-Helix Proteins; D003577:Cytochrome P-450 Enzyme System; D004147:Dioxins; D004785:Environmental Pollutants; D005419:Flavonoids; D006841:Hydrocarbons, Aromatic; D006846:Hydrocarbons, Halogenated; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D015262:Xenobiotics; D000099162:Endothelial PAS Domain-Containing Protein 1