Linear ubiquitination signals in adaptive immune responses.
Linear ubiquitination signals in adaptive immune responses.
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DOI：
10.1111/imr.12300
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发表时间：
2015-07
影响因子：
8.7
通讯作者：
Ikeda F
中科院分区：
文献类型：
--
作者：
Ikeda F
泛素可以使用固有的Met 1残基或七个固有的Lys残基之一来形成八种不同的连接类型的链。每种连接类型的泛素链都具有独特的三维拓扑结构，作为标签吸引特定的信号分子，这些信号分子被称为泛素阅读器，并调节各种生物学功能。通过Met 1以头-尾方式连接的泛素链称为线性泛素链。线性泛素化在细胞信号传导的调节中起重要作用，包括最具特征的肿瘤坏死因子（TNF）诱导的经典核因子-κ B（NF-κB）途径。线性泛素链由称为线性泛素链组装复合物（LUBAC）的E3连接酶复合物特异性产生，并由称为具有线性连接特异性的卵巢肿瘤（OTU）DUB（OTULIN）的去泛素酶（DUB）水解。LUBAC线性泛素化TNF途径中的关键分子，如NEMO和RIPK 1。线性泛素链然后被泛素阅读器识别，包括控制TNF途径的NEMO。越来越多的证据表明LUBAC复合物在调节小鼠的细胞凋亡、发育和炎症中的重要性。在这篇文章中，我专注于线性泛素链在适应性免疫反应中的作用，重点是TNF诱导的信号通路。
Ubiquitin can form eight different linkage types of chains using the intrinsic Met 1 residue or one of the seven intrinsic Lys residues. Each linkage-type of ubiquitin chain has a distinct three-dimensional topology, functioning as a tag to attract specific signaling molecules, which are so-called ubiquitin readers, and regulates various biological functions. Ubiquitin chains linked via Met 1 in a head-to-tail manner are called linear ubiquitin chains. Linear ubiquitination plays an important role in the regulation of cellular signaling, including the best-characterized Tumor Necrosis Factor (TNF) -induced canonical nuclear factor-kappa B (NF-κB) pathway. Linear ubiquitin chains are specifically generated by an E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) and hydrolyzed by a deubiquitinase (DUB) called ovarian tumor (OTU) DUB with linear linkage specificity (OTULIN). LUBAC linearly ubiquitinates critical molecules in the TNF pathway, such as NEMO and RIPK1. The linear ubiquitin chains are then recognized by the ubiquitin readers, including NEMO, which control the TNF pathway. Accumulating evidence indicates an importance of the LUBAC complex in the regulation of apoptosis, development, and inflammation in mice. In this article, I focus on the role of linear ubiquitin chains in adaptive immune responses with an emphasis on the TNF-induced signaling pathways.