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

基本信息

批准号：
9209454
负责人：
Amy E Ikui
金额：
$ 36.69万
依托单位：
BROOKLYN COLLEGE
依托单位国家：
美国
项目类别：
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/9209454
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 A 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 kinase inhibitor mutant novel pathogen polarized cell prevent response sensor time use tumorigenesis

项目摘要

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.

项目摘要/摘要酵母细胞需要快速控制其细胞周期谱，基因表达或蛋白质应力反应途径激活的稳定性。细胞很常见遭受对质膜和细胞壁的各种攻击，例如身体损伤，病原体入侵和各种环境扰动。在这里我们建议学习质膜应激通过新细胞周期抑制细胞的生长和DNA复制检查点途径。真核细胞复制其染色体。 DNA中的错误复制控制可能导致染色体不稳定性，这是癌症的标志。我们的长期术语目标是理解响应于DNA复制控制的分子机制压力。在此提案中，如果质膜损坏，三个目标将检验我的假设通过新的细胞周期检查点抑制极化细胞的生长和DNA复制路径。 AIM1将确定膜损伤如何驱动PKC1迁移到抑制极化细胞生长。 AIM2将确定质膜应力信号如何激活MPK1以抑制DNA 复制。 AIM3将确定酵母GSK-3激酶MCK1是否在等离子体上靶向复制蛋白膜应力从酵母到人类，DNA复制和膜完整性途径是充分保守的。从这项研究获得的结果可以应用于了解的分子机制 DNA复制控制响应较高的真核生物的应力。