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 卤代芳烃（HAH），广泛存在， 持久性环境污染物。暴露于TCDD的动物表现出 一系列毒性作用，包括代谢途径的改变， 免疫学变化、致畸作用和瘤形成。 流行病学研究表明，接触TCDD会导致皮肤 病变和可能增加的风险，为某些形式的癌症在人类 人口 Ah（芳烃）受体（AhR）是bHLH转录因子 它与其他蛋白质一起，介导 TCDD。该项目的总体目标是确定新的蛋白质 Ah受体的伴侣。本研究的具体目的是：（1） 识别受体的功能结构域，重点是 负责结合HLH蛋白，转录激活， 和转录抑制;（2）鉴定、克隆和 蛋白质（Arnt除外）的表征， 调节Ah受体的功能。 这项研究将提供一个更好的了解机制， TCDD在体内发挥其生物学效应。这些知识并 有助于解决在评估TCDD造成的风险方面的不确定性， 人体健康

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.