Identification and function of posttranslational modifications in the Dioxin Receptor/Arnt transcription factor

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Polycyclic aromatic hydrocarbons (PAHs) are prevalent environmental pollutants which cause a wide range of deleterious health effects. Metabolic activation of PAHs occurs primarily through a set of intracellular oxidising enzymes which are induced by the presence of PAHs. The dioxin receptor is a gene regulatory protein that is pivotal in the metabolic pathway as it links the presence of contaminating PAHs to induction of the enzymes responsible for initiating their metabolism. While in many cases PAHs are oxidised to compounds which are water soluble and excretable (and therefore harmless), some substrates, such as benzo[a]pyrene found in cigarette smoke, can become inadvertently transformed into carcinogens. Other pollutants such as dioxin are resistant to metabolism and are extremely toxic. We have an ongoing interest in deciphering the biochemical pathways which lead to aberrant metabolism, and as such are studying the mechanistic role of the dioxin receptor in this process.