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: 2187254
• 负责人: FREDERICK R. CROSS
• 金额: $ 16.13万
• 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/2187254
• 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.

在细胞周期的GL相中发芽的酵母伴侣。 每个细胞 交配类型会产生与细胞表面相互作用的交配信息素 相反交配类型的细胞上的受体。信息素与 受体触发一个区分程序，包括改变基因 转录，细胞形态改变和GL细胞周期停滞。这 在细胞周期的GL阶段开始调节点标记了一个尖锐的 从灵敏度到交配信息素到抵抗力直至过渡 下一个GL阶段。 我们对此的分子基础感兴趣 承诺事件，集成了共轭和细胞周期。 这 FAR1基因对于交配信息素停滞至关重要。我们发现 FAR1降解受细胞周期调节，降解与 磷酸化。此控制和FAR1转录控制导致 仅在启动前的GL相中，FAR1蛋白的显着积累 细胞周期。因此，FAR1的细胞周期调节可以有助于 从一开始，从交配信息素敏感性到抗性的过渡。 这 暗示涉及的机械上的细胞周期进程对负面控制 在细胞周期停滞和交配中。 我们已经开始遗传和生化 分析控制FAR1降解的基础。 这个分析 基于我们的观察结果，即Far1磷酸化之前 降解，以及far1块的N末端缺失突变体 降解。 我们已经确定了额外的独立负面 控制整体信息素信号通路。转录 涉及交配的基因的交配因子的诱导在很大程度上被阻止 大约开始时，可​​能是特定的CLN/CDC28蛋白激酶 复合物。我们希望以遗传和 最终在生化上。