Cell cycle regulation in response to plasma membrane stress in S. cerevisae

酿酒酵母质膜应激的细胞周期调节

• 批准号: 9897602
• 负责人: Amy E Ikui
• 金额: $ 35.33万
• 依托单位: BROOKLYN COLLEGE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9897602
• 关键词: Biological Assay; CDK2 gene; Cell Cycle; Cell Cycle Arrest; Cell Cycle Checkpoint; Cell Cycle Regulation; Cell Wall; Cell membrane; Cell surface; Cells; Chromosomal Instability; Chromosomes; Consensus; Consensus Sequence; Cyclin-Dependent Kinase Inhibitor; Cyclin-Dependent Kinases; Cyclins; DNA; DNA biosynthesis; Eukaryota; Eukaryotic Cell; Failure; Fluorescence Microscopy; G1 Phase; Gene Expression; Gene Proteins; Genes; Glycogen Synthase Kinase 3; Goals; Growth; Human; In Vitro; Lead; Link; Malignant Neoplasms; Membrane; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Molecular; Monomeric GTP-Binding Proteins; Organism; PRKCA gene; Pathway interactions; Phenotype; Phosphorylation; Phosphorylation Site; Phosphotransferases; Plasma Cells; Population Growth; Protein Dephosphorylation; Protein Kinase C; Proteins; Signal Transduction; Site; Stress; Structure; Testing; Transcriptional Activation; Two-Hybrid System Techniques; Yeasts; biological adaptation to stress; cell growth; environmental change; mutant; novel; pathogen; polarized cell; prevent; response; sensor; time use; tumorigenesis

Project Summary/Abstract Yeast cells need to rapidly control their cell cycle profile, gene expression or protein stability in response to the activation of stress response pathways. It is common for cells to suffer from various attacks to their plasma membrane and cell wall, such as physical damage, pathogen invasion and various environmental perturbations. Here we propose to study that plasma membrane stress inhibits cell growth and DNA replication through a novel cell cycle checkpoint pathway. Eukaryotic cells duplicate their chromosomes. Errors in the DNA replication control could lead to chromosome instability which is a hallmark of cancer. Our long- term goal is to understand the molecular mechanism of DNA replication control in response to stress. In this proposal, three aims will test my hypothesis if plasma membrane damage inhibits polarized cell growth and DNA replication through a novel cell cycle checkpoint pathway. Aim1 will determine how membrane damage drives Pkc1 relocation to inhibit polarized cell growth. Aim2 will determine how plasma membrane stress signal activates Mpk1 to inhibit DNA replication. Aim3 will determine if a yeast GSK-3 kinase Mck1 targets replication proteins upon plasma membrane stress DNA replication and membrane integrity pathways are well conserved from yeast to humans. The results obtained from this study can be applied to understand the molecular mechanism of DNA replication control in response to stress in higher eukaryotes.

项目总结/摘要 酵母细胞需要快速控制其细胞周期谱、基因表达或蛋白质 稳定性响应于应激反应途径的激活。细胞通常 它们的质膜和细胞壁遭受各种攻击，例如物理损伤， 病原体入侵和各种环境扰动。在这里，我们建议研究 质膜应激通过一种新的细胞周期抑制细胞生长和DNA复制 检查点途径。真核细胞复制它们的染色体。DNA中的错误 复制控制可能导致染色体不稳定，这是癌症的标志。我们长久以来- 本学期的目标是了解DNA复制控制的分子机制， 应力 在这个建议中，三个目标将测试我的假设，如果质膜损伤 通过新的细胞周期检查点抑制极化细胞生长和DNA复制 通路 Aim 1将决定膜损伤如何驱动Pkc 1重新定位以抑制极化细胞 增长 Aim 2将决定质膜应激信号如何激活Mpk 1以抑制DNA 复制的 Aim 3将确定酵母GSK-3激酶Mck 1是否靶向血浆中的复制蛋白 薄膜应力 从酵母到人类，DNA复制和膜完整性途径都很保守。 本研究的结果可用于理解细胞凋亡的分子机制。 高等真核生物对胁迫的DNA复制控制。