INTEGRATION OF MATING WITH THE BUDDING YEAST CELL CYCLE

交配与出芽酵母细胞周期的整合

• 批准号: 2187255
• 负责人: FREDERICK R. CROSS
• 金额: $ 19.23万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2187255
• 关键词: Saccharomyces cerevisiae; biological signal transduction; cell cycle; cell cycle proteins; enzyme induction /repression; fungal genetics; gene expression; genetic transcription; microorganism conjugation; microorganism reproduction; oligonucleotides; pheromone; protein kinase

Budding yeast mate in the Gl phase of the cell cycle. Cells of each mating type produce mating pheromones that interact with cell surface receptors on cells of the opposite mating type. Binding of pheromone to receptors triggers a differentiative program including altered gene transcription, altered cell morphology, and Gl cell cycle arrest. The START regulatory point in the Gl phase of the cell cycle marks a sharp transition from sensitivity to mating pheromones to resistance until the next Gl phase. We are interested in the molecular basis of this commitment event, which integrates conjugation and the cell cycle. The FAR1 gene is essential for mating pheromone arrest. We have found that FAR1 degradation is cell-cycle regulated, and degradation correlates with phosphorylation. This control and FAR1 transcriptional control result in significant accumulation of Far1 protein only in the pre-START Gl phase of the cell cycle. Cell cycle regulation of FAR1 thus can contribute to the transition from mating pheromone sensitivity to resistance at START. This implies a negative control by cell-cycle progression on machinery involved in cell cycle arrest and mating. We have begun genetic and biochemical analysis of the basis for the control of Far1 degradation. This analysis is based on our observations that Far1 phosphorylation precedes its degradation, and that an N-terminal deletion mutant of Far1 blocks degradation. We have identified an additional independent negative control of the overall pheromone signalling pathway. Transcriptional induction by mating factor of genes involved in mating is largely blocked at about the time of START, possibly by specific Cln/Cdc28 protein kinase complexes. We wish to characterize this control, first genetically and ultimately biochemically.

芽殖酵母在细胞周期的G1期交配。 每个细胞 交配型产生交配信息素与细胞表面相互作用 相反交配类型的细胞上的受体。信息素与 受体触发分化程序，包括改变基因 转录、改变的细胞形态和G1细胞周期停滞。的 START调节点在细胞周期的G1期标志着一个急剧的 从敏感性到交配信息素再到抗性的转变， 下一个GI期。 我们感兴趣的是它的分子基础 承诺事件，整合接合和细胞周期。 的 FAR 1基因是交配信息素阻滞所必需的。我们发现 FAR 1降解受细胞周期调节，并且降解与 磷酸化这种控制和FAR 1转录控制导致 Far 1蛋白仅在STARTG 1期前显著积累， 细胞周期因此，FAR 1的细胞周期调节可以有助于 从交配信息素敏感性到抗性的转变。 这 意味着细胞周期进程对相关机制的负控制 在细胞周期停滞和交配中。 我们已经开始从遗传学和生物化学 分析控制Far 1降解的依据。 该分析 是基于我们的观察，Far 1磷酸化先于其 降解，并且Far 1的N-末端缺失突变体阻断了 降解 我们发现了另外一个独立的阴性 控制整个信息素信号通路。转录 交配因子对参与交配的基因的诱导作用在很大程度上被阻断 在大约开始时，可能通过特异性Cln/Cdc 28蛋白激酶 配合物我们希望描述这种控制，首先从遗传学上， 最后是生物化学。