Linear ubiquitination in immunity.
Linear ubiquitination in immunity.
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DOI：
10.1111/imr.12309
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发表时间：
2015-07
影响因子：
8.7
通讯作者：
Walczak H
中科院分区：
文献类型：
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作者：
Shimizu Y;Taraborrelli L;Walczak H
线性泛素化是最近发现的一种翻译后蛋白质修饰，对先天性和获得性免疫信号至关重要。线性泛素链的功能在多个水平上受到调节：生成、识别和移除。这些链是由线性泛素链组装复合体(LUBAC)产生的，LUBAC是唯一已知的能够从头形成线性泛素链的泛素E3。LUBAC不仅与核因子-κB(NF-κB)和丝裂原激活蛋白激酶(MAPK)在各种信号通路中的激活有关，而且重要的是，它还调节能够诱导这种反应的免疫受体下游的细胞死亡。对线性泛素连接的识别是由某些泛素受体特异性地介导的，这对于翻译成预期的信号输出是至关重要的。LUBAC缺乏会导致基因激活减弱和细胞死亡增加，从而导致小鼠和人类的病理状态。泛素链的去除是由脱泛素酶(DUBS)介导的。其中两个，OTULIN和CyLD，与LUBAC密切相关。在这里，我们综述了免疫信号通路中线性泛素化的现有知识，以及线性泛素如何发挥其有别于其他泛素连接类型的功能的生化机制。
Linear ubiquitination is a post‐translational protein modification recently discovered to be crucial for innate and adaptive immune signaling. The function of linear ubiquitin chains is regulated at multiple levels: generation, recognition, and removal. These chains are generated by the linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin E3 capable of forming the linear ubiquitin linkage de novo. LUBAC is not only relevant for activation of nuclear factor‐κB (NF‐κB) and mitogen‐activated protein kinases (MAPKs) in various signaling pathways, but importantly, it also regulates cell death downstream of immune receptors capable of inducing this response. Recognition of the linear ubiquitin linkage is specifically mediated by certain ubiquitin receptors, which is crucial for translation into the intended signaling outputs. LUBAC deficiency results in attenuated gene activation and increased cell death, causing pathologic conditions in both, mice, and humans. Removal of ubiquitin chains is mediated by deubiquitinases (DUBs). Two of them, OTULIN and CYLD, are constitutively associated with LUBAC. Here, we review the current knowledge on linear ubiquitination in immune signaling pathways and the biochemical mechanisms as to how linear polyubiquitin exerts its functions distinctly from those of other ubiquitin linkage types.