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

二恶英受体/Arnt转录因子翻译后修饰的鉴定和功能

• 批准号: nhmrc : 299053
• 负责人: Prof Jeffrey Gorman
• 金额: $ 29.91万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/identification-function-posttranslational-transcription-factor/95147
• 关键词: Identification; function; posttranslational; modifications; Dioxin

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.

多环芳烃（PAHs）是一种普遍存在的环境污染物，对人体健康有着广泛的危害。多环芳烃的代谢活化主要是通过一组细胞内氧化酶发生的，这些酶是由多环芳烃的存在诱导的。二恶英受体是一种基因调节蛋白，在代谢途径中起关键作用，因为它将污染多环芳烃的存在与负责启动其代谢的酶的诱导联系起来。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（因此是无害的），但一些底物，如香烟烟雾中发现的苯并[a]芘，可能会无意中转化为致癌物。其他污染物如二恶英，则具有抗代谢性，毒性极强。我们一直有兴趣破译导致异常代谢的生化途径，因此正在研究二恶英受体在这一过程中的机制作用。