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HORMONE REGULATION--VITELLOGENIN & LIPOPROTEIN SYNTHESI

激素调节--卵黄原素

基本信息

批准号：
3151123
负责人：
DAVID LEE WILLIAMS
金额：
$ 22.53万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-02-01 至 1990-01-31
项目状态：
已结题

项目摘要

This research concerns the hormonal regulation of the vitellogenins and the apolipoproteins of very low density lipoprotein. These proteins are synthesized in the avian liver in response to estrogenic stimulation and serve to transport lipid and other nutrients to the yolk for embryonic development. These proteins are of great interest as models for the study of estrogen action and because of their roles in lipid transport. This proposal is largely focused on the regulation of apolipoprotein II (apo II) gene expression. Apo II is a major protein component of the very low density lipoprotein particles synthesized in response to estrogen. The estrogen-stimulated synthesis of apo II involves activation of gene transcription and a marked cytoplasmic stabilization of apo II mRNA. Experiments will be carried out to examine the estrogen-mediated stabilization of apo II mRNA and to test the hypothesis that stabilization is due to site specific interactions between stabilization factors and apo II mRNA. The research will be directed to three major questions. First, how is apo II mRNA structure related to functional aspects of its expression? These studies will require elucidation of the heterogeneity found at the 5' and 3' ends of the mRNA and an analysis of apo II mRNA secondary structure. A new method for high resolution mapping of mRNAs with base and struture specific ribonucleases has been developed for this purpose. Second, What is the pattern of protein binding on the mRNA and how does it relate to secondary structure and stabiliztion of apo II mRNA? Nuclease mapping will be used to determine sequences that are altered as a result of interaction with protein. Third, do apo II messenger ribonucleoprotein particles contain proteins unique to this mRNA? Are such proteins involved in estrogen-mediated stabilization. These particles will be purified and the proteins analyzed. Monoclonal antibodies to apo II mRNP proteins will be used to determine which proteins are unique to apo II mRNA, which are common to etrogen-regulated mRNAs, and which are common to all mRNAs. The long-term goal is to understand how estrogen-mediated stabilization of mRNA occurs. This is a major action of estrogens that has received relatively little attention.

本研究涉及卵黄原蛋白的激素调节和极低密度脂蛋白的载脂蛋白。这些蛋白质响应雌激素刺激在禽类肝脏中合成，为胚胎运输脂质和其他营养物质到蛋黄发展这些蛋白质作为研究的模型具有很大的意义雌激素的作用，因为它们在脂质运输中的作用。这该提案主要集中在载脂蛋白II（apo II）的调节上基因表达。载脂蛋白II是一种非常低的蛋白质组分，密度脂蛋白颗粒的合成对雌激素的反应。的雌激素刺激的载脂蛋白II合成涉及基因激活转录和显着的apo II mRNA的细胞质稳定。将进行实验以检查雌激素介导的稳定载脂蛋白II mRNA，并检验稳定化是由于稳定因子和载脂蛋白之间的位点特异性相互作用 II mRNA。该研究将针对三个主要问题。第一、载脂蛋白II mRNA的结构与其功能方面是如何相关的？表情？这些研究将需要阐明异质性在mRNA的5'和3'末端发现，二级结构。一种新的高分辨率基因定位方法具有碱基和结构特异性的核糖核酸酶已经为此开发出来。目的. 第二，蛋白质结合在mRNA上的模式是什么，它与载脂蛋白II mRNA的二级结构和稳定性有什么关系？核酸酶图谱将用于确定作为一种酶被改变的序列。与蛋白质相互作用的结果。三、做载脂蛋白II信使核糖核蛋白颗粒含有这种mRNA特有的蛋白质？真是参与雌激素介导的稳定的蛋白质。这些颗粒将进行纯化和蛋白质分析。抗载脂蛋白II单克隆抗体 mRNP蛋白将用于确定哪些蛋白是apo II所特有的 mRNA，这是共同的雌激素调节的mRNA，这是共同的，所有的mRNA。长期目标是了解雌激素介导的 mRNA的稳定化发生。这是雌激素的主要作用，受到的关注相对较少。