STUDIES OF PROTEINS INVOLVED IN CHILDHOOD LEUKEMIAS: ALONE AND WITH INHIBITORS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。泛素和泛素样蛋白的翻译后共价连接已成为一种主要的细胞调控机制，在控制细胞分裂、信号转导、胚胎发育、内吞转运和免疫反应等方面发挥着重要作用。因此，泛素样修饰途径的解除调控在许多疾病中发挥了作用，包括癌症、出生缺陷和帕金森S病，几种病毒在感染期间劫持了这些途径。泛素样蛋白通过重塑其目标蛋白的表面、改变其目标S的半衰期、酶活性、蛋白质/蛋白质相互作用、亚细胞定位或其他性质来发挥作用。我们正在试图了解用泛素和泛素样蛋白标记蛋白质底物的酶的机制。除了努力了解泛素样蛋白转移的基本原理外，我们还在研究泛素途径中涉及的蛋白质的结构，泛素途径在圣犹大儿童S研究医院治疗的儿童癌症中发挥作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Post-translational covalent attachment of ubiquitin and ubiquitin-like proteins has emerged as a predominant cellular regulatory mechanism, with important roles in controlling cell division, signal transduction, embryonic development, endocytic trafficking and the immune response. As a result, deregulation of the pathways for attaching ubiquitin-like modifications plays a role in a number of diseases, including cancer, birth defects and Parkinson¿¿s Disease, and several viruses hijack these pathways during infection. Ubiquitin-like proteins function by remodelling the surface of their target proteins, changing their target¿¿s half-life, enzymatic activity, protein/protein interactions, subcellular localization or other properties. We are trying to understand the mechanisms of enzymes that tag protein substrates with ubiquitin and ubiquitin-like proteins. In addition to our efforts to understand the basic principles governing ubiquitin-like protein transfer, we are studying the structures of proteins involved in the ubiquitin pathway that play a role in childhood cancers treated at St. Jude Children¿¿s Research Hospital.