DIOXIN ACTION--NEW PROTEIN PARTNERS FOR THE AH RECEPTOR

2，3，7，8-四氯二苯并对二恶英是一组 广泛存在的卤代芳香烃(HAH) 持久性环境污染物。暴露于TCDD的动物表现出 一系列的毒性作用，包括代谢途径的改变， 免疫学变化、致畸作用和肿瘤形成。 流行病学研究表明，接触TCDD会导致皮肤 人类某些形式癌症的损害和可能增加的风险 人口。 芳香烃受体(AhR)是一种bHLH转录因子 它与其他蛋白质一起，介导了 TCDD。拟议项目的总体目标是识别新的蛋白质。 AH受体的合作伙伴。研究的具体目的是：(1) 识别受体的功能结构域，重点是 负责结合促黄体生成素蛋白的结构域(S)，转录激活， 和转录抑制；(2)鉴定、克隆和 与和相互作用的蛋白质(Arnt除外)的特性 调节ah受体的功能。 这项研究将通过以下方式更好地理解这一机制 其中TCDD在体内产生生物效应。这一知识可能 帮助解决评估TCDD带来的风险方面的不确定性 人类健康。

2,3,7,8-Tetrachlorodibenzo-p-dioxin is the prototype of a group of halogenated aromatic hydrocarbons (HAH) that are widespread and persistent environmental pollutants. Animals exposed to TCDD exhibit a range of toxic effects including alterations in metabolic pathways, immunological changes, teratogenic effects, and neoplasia. Epidemiological studies demonstrate that exposure to TCDD causes skin lesions and possibly increased risks for some forms of cancer in human population. Ah (Aromatic hydrocarbon) receptor (AhR) is a bHLH transcription factor which, together with other proteins, mediates the biological effects of TCDD. The overall goal of the proposed project is to identify new protein partners for the Ah receptor. The specific aims of the study are: (1) identification of the receptor's functional domains, with emphasis on domains responsible for binding HLH protein(s), transcription activation, and transcription inhibition; (2) identification, cloning, and characterization of proteins (other than Arnt) that interact with and modulate the functions of the Ah receptor. This research will provide a better understanding of the mechanism by which TCDD elicits its biological effects in vivo. This knowledge may help to resolve uncertainty in assessing the risk that TCDD poses to human health.