Measuring activity in the ubiquitin-proteasome system: from large scale discoveries to single cells analysis.
Measuring activity in the ubiquitin-proteasome system: from large scale discoveries to single cells analysis.
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DOI：
10.1007/s12013-013-9621-9
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发表时间：
2013-09
影响因子：
2.6
通讯作者：
Allbritton, Nancy L.
中科院分区：
文献类型：
--
作者：
Melvin, Adam T.;Woss, Gregery S.;Park, Jessica H.;Waters, Marcey L.;Allbritton, Nancy L.
泛素蛋白酶体系统（UPS）是负责识别和降解错误折叠、受损或严格调节的蛋白质的主要途径，除了在DNA修复、细胞周期调节、细胞迁移和免疫应答中发挥重要作用之外。虽然传统的生物化学技术已被证明可用于鉴定参与该途径的关键蛋白质，但负责测量UPS酶活性的新型报告物的实现为UPS在各种人类疾病如多发性骨髓瘤和亨廷顿病中的治疗效果和作用提供了有价值的见解。这些报告基因通常由与分析手柄融合的识别序列组成，旨在特异性评价UPS某些成员的酶活性，包括蛋白酶体、E3泛素连接酶和去泛素化酶（DUB）。这篇综述强调了更常用的记者在各种情况下，从高通量筛选新的抑制剂单细胞显微镜技术测量E3连接酶或蛋白酶体活性。最后，最近的工作是突出开发新的degron为基础的基板，旨在克服目前的报告技术的局限性，在测量E3连接酶和蛋白酶体活性的患者样本。
The ubiquitin proteasome system (UPS) is the primary pathway responsible for the recognition and degradation of misfolded, damaged, or tightly regulated proteins in addition to performing essential roles in DNA repair, cell cycle regulation, cell migration, and the immune response. While traditional biochemical techniques have proven useful in the identification of key proteins involved in this pathway, the implementation of novel reporters responsible for measuring enzymatic activity of the UPS have provided valuable insight into the effectiveness of therapeutics and role of the UPS in various human diseases such as multiple myeloma and Huntington’s disease. These reporters, usually consisting of a recognition sequences fused to an analytical handle, are designed to specifically evaluate enzymatic activity of certain members of the UPS including the proteasome, E3 ubiquitin ligases, and deubiquitinating enzymes (DUBs). This review highlights the more commonly used reporters employed in a variety of scenarios ranging from high-throughput screening of novel inhibitors to single cell microscopy techniques measuring E3 ligase or proteasome activity. Finally, recent work is presented highlighting the development of novel degron-based substrate designed to overcome the limitations of current reporting techniques in measuring E3 ligase and proteasome activity in patient samples.
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影响因子：
3.7
作者：
Cook C;Gass J;Dunmore J;Tong J;Taylor J;Eriksen J;McGowan E;Lewis J;Johnston J;Petrucelli L
通讯作者：
Petrucelli L
影响因子：
2.6
作者：
Houser, John R.;Ford, Eintou;Errede, Beverly
通讯作者：
Errede, Beverly
影响因子：
3.4
作者：
Jiang, Dechen;Sims, Christopher Eldridge;Allbritton, Nancy Lynn
通讯作者：
Allbritton, Nancy Lynn
影响因子：
--
作者：
Ausseil, Frederic;Samson, Arnaud;Bailly, Christian
通讯作者：
Bailly, Christian
影响因子：
56.9
作者：
BACHMAIR, A;FINLEY, D;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A