Genome-wide YFP Fluorescence Complementation Screen Identifies New Regulators for Telomere Signaling in Human Cells
Genome-wide YFP Fluorescence Complementation Screen Identifies New Regulators for Telomere Signaling in Human Cells
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DOI：
10.1074/mcp.m110.001628
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发表时间：
2011-02-01
影响因子：
7
通讯作者：
Zhou Songyang
中科院分区：
文献类型：
--
作者：
Lee, Ok-Hee;Kim, Hyeung;Zhou Songyang
检测低亲和力或瞬态相互作用可能是我们理解信号网络的瓶颈。为了解决这一问题，我们开发了一种基于蛋白质互补的排列筛选策略，系统地研究了活细胞中蛋白质-蛋白质相互作用，并对端粒调节因子进行了大规模筛选。脊椎动物端粒的维持需要端粒相互作用组成员的协同作用，端粒相互作用组建立在六个核心端粒蛋白TRF1、TRF2、RAP1、TIN2、TPP1和POT1之上。在12000种人类蛋白质中，我们发现了300多种与6种核心端粒蛋白相关的蛋白质。大多数鉴定的蛋白质以前没有与端粒生物学联系，包括翻译后修饰的调节因子，如蛋白激酶和泛素E3连接酶。本研究的结果揭示了人类端粒调控的基础分子生态位，并为研究哺乳动物细胞中的信号通路提供了有价值的工具。分子与细胞蛋白质组学[j] .北京：北京大学学报（自然科学版），2011。
Detection of low-affinity or transient interactions can be a bottleneck in our understanding of signaling networks. To address this problem, we developed an arrayed screening strategy based on protein complementation to systematically investigate protein-protein interactions in live human cells, and performed a large-scale screen for regulators of telomeres. Maintenance of vertebrate telomeres requires the concerted action of members of the Telomere Interactome, built upon the six core telomeric proteins TRF1, TRF2, RAP1, TIN2, TPP1, and POT1. Of the similar to 12,000 human proteins examined, we identified over 300 proteins that associated with the six core telomeric proteins. The majority of the identified proteins have not been previously linked to telomere biology, including regulators of post-translational modifications such as protein kinases and ubiquitin E3 ligases. Results from this study shed light on the molecular niche that is fundamental to telomere regulation in humans, and provide a valuable tool to investigate signaling pathways in mammalian cells. Molecular & Cellular Proteomics 10:10.1074/mcp.M110.001628, 1-11, 2011.