Poly-ubiquitination in TNFR1-mediated necroptosis.
Poly-ubiquitination in TNFR1-mediated necroptosis.
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DOI：
10.1007/s00018-016-2191-4
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Walczak H
中科院分区：
文献类型：
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作者：
Dondelinger Y;Darding M;Bertrand MJ;Walczak H
肿瘤坏死因子（TNF）是一种主要的促炎细胞因子，并且不适当的TNF信号传导与许多炎性疾病的病理学有关。TNF与其受体TNFR1的连接诱导初级膜结合信号复合物的瞬时形成，称为复合物I，其驱动促存活基因的表达。有缺陷的复合物I活化导致细胞凋亡或坏死性凋亡形式的细胞死亡的诱导。这种转换通过复合物I组分的内化以及次级细胞质死亡复合物（分别称为复合物II和坏死体）的组装和活化而发生。在这篇综述中，我们讨论了至关重要的调控功能的泛素化的翻译后蛋白质修饰组成的泛素的共价连接，及其倍数，靶蛋白的TNFR1信号的各个步骤，导致坏死性凋亡。
Tumor necrosis factor (TNF) is a master pro-inflammatory cytokine, and inappropriate TNF signaling is implicated in the pathology of many inflammatory diseases. Ligation of TNF to its receptor TNFR1 induces the transient formation of a primary membrane-bound signaling complex, known as complex I, that drives expression of pro-survival genes. Defective complex I activation results in induction of cell death, in the form of apoptosis or necroptosis. This switch occurs via internalization of complex I components and assembly and activation of secondary cytoplasmic death complexes, respectively known as complex II and necrosome. In this review, we discuss the crucial regulatory functions of ubiquitination—a post-translational protein modification consisting of the covalent attachment of ubiquitin, and multiples thereof, to target proteins—to the various steps of TNFR1 signaling leading to necroptosis.