Regulation and function of yeast transcr#itional activator ADR1

本研究的目的是阐明真核基因调控的机制。所选择的研究系统是酵母转录激活剂ADR1，它控制葡萄糖可抑制酒精脱氢酶(ADH2)。重点是确定ADR1的调控机制，ADR1的功能区，调节或影响ADR1功能的因素，以及这些因素和ADR控制ADH2转录的方式。将使用生化、重组DNA和遗传分析的组合。ADR1的体内磷酸化位点将被确定，cAMP依赖(CAPK)和非依赖的蛋白激酶在ADR1调节中的作用将被确定。ADR1的识别机制。将分离ADR1蛋白，并确定其对转录激活、甘油生长调节、寡聚、血糖控制和小体诱导至关重要的区域。结合或介导ADR1作用的蛋白质将进行生化和遗传学研究。ADR1激活ADH2转录所需的SAF1-3基因将被克隆和测序。CCR1和SCH9蛋白激酶的作用也将被确定，它们独立于ADR1控制ADH2。

The goal of this research is to elucidate the mechanisms of eucaryotic gene regulation. The system chosen for study is the yeast transcriptional activator ADR1 in its control of glucose repressible alcohol dehydrogenase (ADH2). Particular emphasis will be placed on defining the mechanisms by which ADR1 is regulated, the functional regions of ADR1, the factors which mediate or influence ADR1 function, and the means by which these factors and ADR control ADH2 transcription. A combination of biochemical, recombinant DNA, and genetic analyses will be used. The in vivo phosphorylation site of ADR1 will be identified and the role of cAMP-dependent (cAPK) and -independent protein kinases in ADR1 regulation will be ascertained. The mechanisms by which ADR1 will be identified. The ADR1 protein will be isolated and its regions important to transcriptional activation, regulation of glycerol growth, oligomerization, glucose control, and induction of petites will be identified. The proteins which bind to or mediate ADR1 action will be studied biochemically and genetically. The SAF1-3 genes required for ADR1 activation of ADH2 transcription will be cloned and sequenced. The role of the CCR1 and SCH9 protein kinases which act independently of ADR1 controlling ADH2 will also be determined.