ABSTRACT The aryl hydrocarbon receptor (AHR) is traditionally characterized as a transcription factor that mediates mammalian responses to xenobiotics, namely polyaromatic halogenated (PAH) compounds. The receptor has been a focal point of toxicological research for several decades due to its central role in dioxin and other PAH induced toxicity. The resulting body of work depicts a receptor that not only functions as a ligand-activated transcription factor, but also as one that can influence several different signaling pathways and cellular processes through direct protein:protein interaction. In fact, the diverse functions of the AHR suggest it could be classified as a moonlighting protein. Moonlighting proteins are characterized by their multifunctional cellular roles and include glycolytic enzymes and several cytochrome P450 monooxygenases. Here we review the various cellular functions of the AHR, including its ability to influence transcription, directly and indirectly, and its ability to influence immunity, cell cycle and mitochondrial function via protein:protein interaction. These distinct functions imply that the AHR can be identified as a moonlighting protein.
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