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The KSHV Ubiquitome: Developing a CURE (Course-based undergraduate research experience)

KSHV Ubiquitome：开发 CURE（基于课程的本科研究经验）

基本信息

批准号：
10529566
负责人：
Elana S Ehrlich
金额：
$ 39.74万
依托单位：
TOWSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10529566
关键词：
KSHV Ubiquitome Developing CURE Course

项目摘要

ABSTRACT Ubiquitin and ubiquitin like (Ubl) proteins such as SUMO-1 and SUMO-2/3 have wide ranging effects on protein stability, localization, interactions, and overall function. Many viruses have evolved mechanisms to influence cellular processes through manipulation of the ubiquitin proteasome system. Kaposi’s sarcoma herpesvirus (KSHV) encodes proteins with E3 ubiquitin ligase activity, SUMO ligase activity and interacts with the cellular ubiquitin proteasome system, with reported effects on signaling, apoptosis, immune response and cell cycle regulation. KSHV is a human tumor virus associated with three different cancers and two inflammatory syndromes. Both latency and lytic replication play roles in establishing and maintaining disease, therefore it is important to understand the mechanisms that regulate this transition. Our long-term goal is to identify and characterize cellular pathways targeted by KSHV through viral manipulation of the ubiquitin and ubiquitin-like modification systems. This will contribute to our understanding of the cell biology of KSHV infection and enable identification of targets for further study and ultimately intervention. We have carried out a comparative analysis of the ubiquitome in TREx BCBL1 cells as well as cells expressing RTA alone. We have identified 193 differentially ubiquitinated sites in 146 proteins in cells transfected with RTA, 274 sites in 206 proteins in doxycycline treated TREx BCBL1 cells, and 209 sites in 98 proteins in both data sets, representing proteins with RTA induced ubiquitination alterations. In AIM1 of this grant, we propose to carry out validation and initial characterization of our findings in concert with the development of a CURE (course- based undergraduate research experience). In AIM 2, undergraduate and masters students in my laboratory will evaluate outcomes in infected cells in terms of lytic reactivation, genome replication and infectious virus production. These studies will have a significant impact as we will identify and characterize novel strategies of viral evasion and manipulation of host cellular processes while providing undergraduate research experiences to a diverse population of students.

摘要泛素和泛素样（Ubl）蛋白如SUMO-1和SUMO-2/3对细胞凋亡具有广泛的影响。蛋白质稳定性、定位、相互作用和整体功能。许多病毒进化出了通过操纵泛素蛋白酶体系统影响细胞过程。卡波西肉瘤疱疹病毒（KSHV）编码具有E3泛素连接酶活性、SUMO连接酶活性的蛋白质，并与细胞泛素蛋白酶体系统，报道了对信号传导、细胞凋亡、免疫应答和细胞周期调控KSHV是一种人类肿瘤病毒，与三种不同的癌症和两种炎症相关。综合征潜伏期和裂解性复制都在疾病的形成和维持中起作用，因此，重要的是要了解调节这种转变的机制。我们的长期目标是鉴定和表征KSHV通过病毒介导的靶向细胞通路。操纵泛素和泛素样修饰系统。这将有助于我们了解 KSHV感染的细胞生物学，并能够识别进一步研究和最终干预的目标。我们对TREx BCBL 1细胞以及表达BCBL 1的细胞中的泛素组进行了比较分析。 RTA单独。我们已经在用RTA转染的细胞中的146个蛋白质中鉴定了193个差异泛素化位点，在多西环素处理的TREx BCBL 1细胞中，206个蛋白质中有274个位点，两个数据中98个蛋白质中有209个位点集合，代表具有RTA诱导的泛素化改变的蛋白质。在本补助金的目的1中，我们建议我们的研究结果的验证和初步表征与CURE（课程- 本科研究经验）。在AIM 2中，我实验室的本科生和硕士生将评估感染细胞在裂解再活化、基因组复制和感染病毒方面的结果。生产这些研究将产生重大影响，因为我们将识别和表征新的病毒逃避和操纵宿主细胞过程的策略，同时提供本科研究经验，以不同的学生群体。