Generation and physiological roles of linear ubiquitin chains.
Generation and physiological roles of linear ubiquitin chains.
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线性泛素链的产生和生理作用。
DOI：
10.1186/1741-7007-10-23
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发表时间：
2012-03-15
期刊：
影响因子：
5.4
通讯作者：
Dikic I
中科院分区：
文献类型：
--
作者：
Walczak H;Iwai K;Dikic I
泛素化现在与磷酸化一起成为研究最多的蛋白质翻译后修饰之一，在所有生物学中具有广泛的调节作用。泛素化通常涉及向靶蛋白分子添加泛素链，并且这些可能是八种不同类型，其中七种涉及一个泛素分子中的七个内部赖氨酸（K）残基之一与下一个泛素分子的羧基末端双甘氨酸的连接。在第八种，即所谓的线性泛素链中，连接是在与靶蛋白缀合的泛素上的甲硫氨酸的氨基末端氨基基团和引入的泛素的羧基末端羧基基团之间。K48连接的链和K63连接的链的生理作用已得到充分确立，K48连接的链对蛋白质的蛋白酶体降解信号传导至关重要，K63连接的链在DNA修复酶的募集、细胞信号传导和内吞作用中发挥作用。我们在这里集中在线性泛素链，它们是如何组装的，以及三种不同的研究途径如何表明线性泛素化在先天性和适应性免疫以及抑制炎症中的生理作用。
Ubiquitination now ranks with phosphorylation as one of the best-studied post-translational modifications of proteins with broad regulatory roles across all of biology. Ubiquitination usually involves the addition of ubiquitin chains to target protein molecules, and these may be of eight different types, seven of which involve the linkage of one of the seven internal lysine (K) residues in one ubiquitin molecule to the carboxy-terminal diglycine of the next. In the eighth, the so-called linear ubiquitin chains, the linkage is between the amino-terminal amino group of methionine on a ubiquitin that is conjugated with a target protein and the carboxy-terminal carboxy group of the incoming ubiquitin. Physiological roles are well established for K48-linked chains, which are essential for signaling proteasomal degradation of proteins, and for K63-linked chains, which play a part in recruitment of DNA repair enzymes, cell signaling and endocytosis. We focus here on linear ubiquitin chains, how they are assembled, and how three different avenues of research have indicated physiological roles for linear ubiquitination in innate and adaptive immunity and suppression of inflammation.
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