Roles of Chaperone Proteins and Phosphorylation Events in activity of the Dioxin Receptor

多环芳烃(PAHs)是一种普遍存在的环境污染物，对人体健康具有广泛的危害。多环芳烃的代谢激活主要是通过一系列由多环芳烃诱导的细胞内氧化酶来实现的。二恶英受体是一种基因调控蛋白，在代谢途径中起关键作用，因为它将污染的多环芳烃的存在与负责启动其新陈代谢的酶的诱导联系在一起。虽然在许多情况下，多环芳烃被氧化成水溶性和可排泄的化合物(因此无害)，但一些底物，如香烟烟雾中发现的苯并[a]芘，可能会在不经意间转化为致癌物质。其他污染物，如二恶英，会抵抗新陈代谢，具有极强的毒性。我们一直对破译导致异常新陈代谢的生化途径感兴趣，因此正在研究二恶英受体在这一过程中的机制作用。

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.