TRANSCRIPTIONAL REGULATION OF INSECT FERRITIN

铁在许多酶促过程中起着至关重要的作用。然而，在这方面， Fe+3可以催化危险的氧化反应。 因此， 生物已经发展出蛋白质来运输、储存和消化这些物质， 不可或缺但危险的金属。 在脊椎动物中进行的大量研究 将感染和肿瘤的发展与过度的 暴露于铁。脊椎动物的数据表明铁蛋白，一种铁- 结合蛋白，在维持细胞的 分化和恶性细胞中的铁稳态。 调控 铁蛋白的表达主要在转录水平， 水平 目前，激活这个的分子机制 反应仍然未知。 最近的数据表明， 昆虫和脊椎动物铁代谢。昆虫铁的知识 然而，新陈代谢是有限的。 我们的初步数据显示， 转录控制与铁蛋白在细胞中的表达密切相关。 黄热病蚊子埃及伊蚊。 本申请的目的 是剖析埃及伊蚊的转录调控 铁蛋白 为达到这项申请的目的，我们会 追求三个具体目标： 1)获得含有约20个5'端内切酶的基因组克隆。 铁蛋白基因的上游区域， 2)在5'上游区域定位顺式调节元件和/或 在铁蛋白基因内， 3)反式调节因子的部分鉴定。

Iron plays an essential role in numerous enzymatic processes. However, Fe+3 can catalyze dangerous oxidative reactions. Thus, all living organisms have developed proteins to transport, store and scavenge this indispensable yet hazardous metal. Numerous studies in vertebrates have associated the development of infection and neoplasia with excessive exposure to iron. Vertebrate data indicate that ferritin, an iron- binding protein, plays an essential role in the maintenance of cellular iron homeostasis in differentiating and malignant cells. The regulation of ferritin expression in these cases in mainly at the transcriptional level. Currently, the actual molecular machinery that activates this response remains unknown. Recent data attest to similarities between insect and vertebrate iron metabolism. Knowledge of insect iron metabolism however is limited. Our preliminary data indicated that transcriptional control is germane to the expression of ferritin in the yellow fever mosquito Aedes aegypti. The objective of this application is to dissect the transcriptional regulation of the mosquito A.aegypti ferritin. To accomplish the objective of this application, we will pursue three specific aims: 1) Obtain genomic clone containing approximately 20 kilobases of the 5' upstream region of the ferritin gene, 2) Map the cis-regulatory elements at the 5' upstream region and/or within the ferritin gene, 3) Partially identify of trans-regulatory factors.