A physical and functional map of the human TNF-α NF-κB signal transduction pathway
A physical and functional map of the human TNF-α NF-κB signal transduction pathway
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DOI：
10.1038/ncb1086
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发表时间：
2004-02-01
影响因子：
21.3
通讯作者：
Superti-Furga, G
中科院分区：
文献类型：
--
作者：
Bouwmeester, T;Bauch, A;Superti-Furga, G
信号转导途径是功能上相互依赖的蛋白质组的模块化组合物，这些蛋白质以协调的方式起作用，将环境信息转化为表型反应。促炎细胞因子肿瘤坏死因子 (TNF)-α 触发信号级联，汇聚转录因子 NF-κB 的激活，形成许多生理和病理过程的基础。在此，我们通过使用包括串联亲和纯化、液相色谱串联质谱、网络分析和使用 RNA 干扰的定向功能扰动研究在内的综合方法，报告了围绕 32 个已知和候选 TNF-α/NF-kappaB 通路成分的蛋白质相互作用网络的图谱。我们鉴定了 221 个分子关联和 80 个以前未知的相互作用因子，其中包括该通路的 10 个新功能调节剂。该系统方法提供了对 TNF-α/NF-κB 通路逻辑的重要见解，并且通常适用于与人类疾病相关的其他通路。
Signal transduction pathways are modular composites of functionally interdependent sets of proteins that act in a coordinated fashion to transform environmental information into a phenotypic response. The pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha triggers a signalling cascade, converging on the activation of the transcription factor NF-kappaB, which forms the basis for numerous physiological and pathological processes. Here we report the mapping of a protein interaction network around 32 known and candidate TNF-alpha/ NF-kappaB pathway components by using an integrated approach comprising tandem affinity purification, liquid-chromatography tandem mass spectrometry, network analysis and directed functional perturbation studies using RNA interference. We identified 221 molecular associations and 80 previously unknown interactors, including 10 new functional modulators of the pathway. This systems approach provides significant insight into the logic of the TNF-alpha/NF-kappaB pathway and is generally applicable to other pathways relevant to human disease.