REGULATION OF YEAST ORNITHINE DECARBOXYLASE DEGRADATION

控制关键细胞过程的蛋白质，如肿瘤抑制因子 而周期蛋白通常会迅速周转，这是一种有助于 迅速调整他们的水平。鸟氨酸脱羧酶 (ODC)由早期反应基因编码，其过度表达可以 变换单元格。针对ODC的药物正在作为癌症进行临床试验- 治疗和预防药物。哺乳动物的降解率 ODC受到严格控制；特别是下游的多胺 ODC的产物，诱导其降解。其背后的机制 这一点正在得到更好的理解，并涉及ODC与 一种多胺诱导的蛋白质，它通过催化降解 蛋白酶体。类似的机制可能会控制ODC在 发芽酵母S.cervisiae，但很少被探索。为了澄清 规则I的过程将：(1)分离阻碍 监管。(2)鉴定和表征具有以下功能的蛋白质 直接与ODC交互。预计这些研究将 阐明酵母和哺乳动物细胞共有的降解机制。

Proteins that control key cellular processes, such as tumor suppressors and cyclins, commonly turn over rapidly, a property that facilitates prompt adjustments in their levels. The enzyme ornithine decarboxylase (ODC) is encoded by an early-response gene and its over-expression can transform cells. Drugs that target ODC are in clinical trial as cancer- therapeutic and-preventative agents. The degradation rate of mammalian ODC is tightly controlled; in particular, polyamines, the downstream product of ODC, induce its degradation. The mechanisms that underlie this are becoming better understood and involve interaction Of ODC with a polyamine-induced protein, which catalyzes degradation by the proteasome. Similar mechanisms are likely to act to control ODC in the budding yeast S. cervisiae, but have been little explored. To elucidate the process of regulation I will: (1) Isolate mutants that impede regulation. (2) Identify and characterize the function of proteins that directly interact with ODC. It is anticipated that these studies will elucidate degradative mechanisms shared by yeast and mammalian cells.