Polarity Establishment in Yeast

酵母极性的建立

基本信息

批准号：
8578046
负责人：
DANIEL J LEW
金额：
$ 33.6万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-03-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8578046
关键词：
Actins Address Affect Anchorage-Independent Growth Antigen-Presenting Cells Applied Genetics Behavior Biochemical Biological CDC42 gene Cell Polarity Cell Shape Cell-Cell Adhesion Cells Complex Cues Cytoplasm Development Eukaryotic Cell Family Feedback Film Funding Genes Genetic Goals Guanine Nucleotide Dissociation Inhibitors Guanine Nucleotide Exchange Factors Guanosine Triphosphate Guanosine Triphosphate Phosphohydrolases Homebound Persons Human Image Individual Investigation Link Malignant - descriptor Malignant Neoplasms Mammalian Cell Mediating Modeling Molecular Partner in relationship Pathway interactions Pheromone Play Preparation Procedures Process Property Proteins Recording of previous events Recruitment Activity Regulation Research Resolution Role Saccharomyces cerevisiae Saccharomycetales Signal Transduction Site Speed Study models System T-Lymphocyte Vesicle Yeasts base cancer cell cancer therapy cell cortex cell motility cell transformation genetic analysis mathematical model mutant public health relevance rho spatiotemporal tool trafficking wound

项目摘要

DESCRIPTION (provided by applicant): Cdc42 plays a key role in the polarization of cells towards a variety of signals (e.g., T cell polarization towards antigen-presenting cells, fibroblas polarization towards wound sites, or yeast bud formation). Human CDC42 can functionally substitute for its yeast counterpart, suggesting that key functions of Cdc42 have been highly conserved, and the ability to apply genetic, biochemical, and cell biological approaches makes yeast a very powerful system for delineating the mechanism of Cdc42 action in cell polarization. The goal of the proposed research is to understand how Cdc42 polarization is regulated, and how the process is restricted so that cells only form one polarization "front". Cancer cells display alterations of cell shape, cell-cell adhesion, and cell motility (all actin-dependent processes regulated by Cdc42), which are likely to be important for numerous aspects of malignant transformation. Deregulation of Cdc42 in mammalian cells promotes anchorage-independent growth, and is necessary for the morphological changes (as well as anchorage independence) that occur in Ras-transformed cells. Thus, Cdc42 deregulation affects the proliferation as well as the metastatic potential of cancer cells. Understanding the normal regulation and function of Cdc42 is an important first step towards addressing how their misregulation might promote cancer.

描述（由申请人提供）：Cdc42 在细胞向各种信号的极化（例如，T 细胞向抗原呈递细胞的极化、成纤维细胞向伤口部位的极化或酵母芽形成）中发挥关键作用。人类CDC42可以在功能上替代其酵母对应物，这表明Cdc42的关键功能已高度保守，并且应用遗传、生化和细胞生物学方法的能力使酵母成为描述Cdc42在细胞极化中的作用机制的非常强大的系统。拟议研究的目标是了解 Cdc42 极化是如何调节的，以及如何限制该过程以使细胞仅形成一个极化“前沿”。癌细胞表现出细胞形状、细胞间粘附和细胞运动的改变（所有肌动蛋白依赖性过程均受 Cdc42 调节），这可能对恶性转化的许多方面都很重要。哺乳动物细胞中 Cdc42 的失调会促进贴壁依赖性生长，并且对于 Ras 转化细胞中发生的形态变化（以及贴壁独立性）是必要的。因此，Cdc42 失调会影响癌细胞的增殖和转移潜力。了解 Cdc42 的正常调节和功能是解决其错误调节如何促进癌症的重要第一步。