Presidential Faculty Fellow

9553140 O‘Shea酵母的生长是由可获得的营养物质维持的。磷酸盐是必需的营养素。当磷酸盐限制转录时，就会产生酸性磷酸酶。这种分泌的酶能分解有机分子中的磷酸基，产生磷酸根离子。PHO5基因编码磷酸酶；当酵母在含有PI的培养基中生长时，转录被严格抑制。目前已鉴定出该基因的三个正调控因子和两个负调控因子。其中两个阳性调控因子已被证明是与启动子结合的转录调控因子。这两个负调控因子都是必不可少的；缺失任何一个都会导致高水平的基因表达。其中一种是PHO80，它与酵母细胞周期蛋白(调节细胞分裂)同源。另一个负调控因子PHO85是CDC相关的蛋白激酶。只有当酵母生长在高磷环境中时，负性调节剂的复合体才能使转录因子PHO4磷酸化。这种磷酸化与基因抑制有关。在低等电点下的生长导致了一种正调节因子PHO81，抑制了激酶复合体。激酶活性的降低与基因的抑制有关；这是由PHO4的作用辅助的，而PHO4的生化活性尚未确定。酵母需要磷酸盐才能生长和繁殖。当磷酸盐含量较低时，酵母菌会分泌一种特殊的酶，分解含有磷酸盐的有机化合物，以更新供应。研究人员发现，调节这种特殊酶的产生的分子也调节细胞分裂。这是适应环境的一个了不起的例子。使用相同或相似的分子来控制磷酸盐的使用，这是生长和分裂所必需的，也会引导细胞自我繁殖。***

9553140 O'Shea Yeast growth is sustained by the availability of nutrients. Phosphate is a required nutrient. When phosphate is limiting transcription of an acid phosphatase occurs. This enzyme which is secreted hydrolyzes phosphoryl groups of organic molecules to yield phosphate ion. The PHO5 gene encodes the phosphatase; transcription is tightly repressed when yeast are grown in medium containing Pi. Three positive regulators and two negative regulators of the gene have been identified. Two of the positive regulators have been shown to be transcriptional regulators that bind to the promoter. Both of the negative regulators are essential; deletion of either results in high levels of gene expression. One of these, PHO80, is homologous to a yeast cyclin (which regulates cell division). The other negative regulator, PHO85, is a CDC related protein kinase. The complex of negative regulators phosphorylates transcription factor PHO4 only when yeast are grown in high phosphate. This phosphorylation is correlated with gene repression. Growth in low Pi results in one of the positive regulators, PHO81, inhibiting the kinase complex. The reduced activity of the kinase is correlated with derepression of the gene; this is assisted by the action of PHO4 whose biochemical activity is not characterized. %%% Yeast require phosphate to grow and multiply. When phosphate amounts are low the yeast secrete a special enzyme that breaks down organic compounds that contain phosphate to renew the supplies. The investigator has found that the same molecules that regulate the production of the special enzyme also regulate cell division. This is a remarkable example of adaptation to the environment. The use of the same or similar molecules that control phosphate use which is necessary for growth and division also direct the cell to reproduce itself. ***