权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Arrestin proteins mediate microbial cellular adaptation and fungal virulence

抑制蛋白介导微生物细胞适应和真菌毒力

基本信息

批准号：
10612333
负责人：
ANDREW ALSPAUGH
金额：
$ 20.13万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-21 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10612333
关键词：
Adaptor Signaling Protein Antibodies Arrestins Binding Biochemical Biological Assay Biological Process Cell Cycle Progression Cell Wall Cell physiology Cells Cellular Stress Chemicals Co-Immunoprecipitations Cryptococcus Cryptococcus neoformans Cryptococcus neoformans infection Data Disease Environment Epitopes Eukaryota Homeostasis Human Immune Immune response In Vitro Individual Infection Knowledge Label Laboratories Maintenance Mediating Mediator Modeling Modification Mycoses Nutrient availability Pathogenesis Pathogenicity Phenotype Physiological Process Protein Family Proteins Proteomics Regulation Role Series Specificity Stress System Ubiquitin Ubiquitination Variant Virulence Western Blotting antimicrobial biological adaptation to stress comparative experimental study extracellular flexibility host-microbe interactions in vivo loss of function microbial microbial host microorganism mutant novel pathogenic fungus pathogenic microbe pharmacologic protein degradation protein function response translational applications ubiquitin ligase ubiquitin-protein ligase

项目摘要

Abstract In order to effectively cause disease, microorganisms must continuously sense and respond to rapidly changing environments. For microbial pathogens, these adaptive cellular processes include the ability to respond to host-derived stresses. The robustness with which microorganisms regulate these adaptive responses largely determines their ability to survive within the infected host. In the experiments outlined in this proposal, we build upon recent and converging data from our laboratory supporting the importance of protein ubiquitination in microbial host responses. Originally defined for directing proteins for degradation, ubiquitination is increasingly recognized as a means of precise regulation of the localization and function of many target proteins. In the human fungal pathogen Cryptococcus neoformans, we have identified the Rsp5 ubiquitin ligase as a key mediator of stress response and virulence. Our preliminary experiments have begun to define the specific aspects of the pathogenic process that require Rsp5 activity, including cell wall homeostasis and cell cycle progression. Consistent with emerging models of ubiquitination in diverse species, our experimental results suggest that Rsp5 is directed to its protein targets by adaptor proteins, including the arrestin protein family. Our initial in vitro and in vivo experiments indicate that the virulence- associated phenotypes of the C. neoformans rsp5 mutant are likely a composite of individual contribution of altered target protein function. By further defining the microbial ubiquitin ligase / adaptor / target protein axis, we will more deeply explore the mechanisms by which stress-induced cellular responses influence fungal infections.

摘要