E1-L2 activates both ubiquitin and FAT10
E1-L2 activates both ubiquitin and FAT10
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DOI：
10.1016/j.molcel.2007.08.020
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发表时间：
2007-09-21
期刊：
影响因子：
16
通讯作者：
Chen, Zhijian J.
中科院分区：
文献类型：
--
作者：
Chiu, Yu-Hsin;Sun, Qinmiao;Chen, Zhijian J.
泛素化由E11、E2和E3组成的酶级联催化。我们在这里报告的识别EL样蛋白，称为E1-L2，激活泛素和另一个泛素样蛋白，脂肪10。有趣的是，E1-L2可以将泛素转移到Ubc 5和Ubc 13，但不能转移到Ubc 3和E2- 25 K，这表明E1-L2可能专门参与泛素化反应的一个子集。E1-L2在体外与FAT 10形成硫酯，该反应需要E1-L2的活性位点半胱氨酸和FAT 10的C-末端双甘氨酸基序。此外，内源性FAT 10在用肿瘤坏死因子-α（TNF α）和干扰素-γ（IFN γ）刺激的细胞中与E1-L2形成硫酯，其诱导FAT 10表达。通过RNAi沉默E1-L2表达阻断了细胞中FAT 10缀合物的形成。小鼠E1-L2基因缺失导致胚胎死亡，提示E1-L2基因在胚胎发生中起重要作用。
Ubiquitination is catalyzed by a cascade of enzymes consisting of Ell, E2, and E3. We report here the identification of an El-like protein, termed E1-L2, that activates both ubiquitin and another ubiquitin-like protein, FAT10. Interestingly, E1-L2 can transfer ubiquitin to Ubc5 and Ubc13, but not Ubc3 and E2-25K, suggesting that E1-L2 may be specialized in a subset of ubiquitination reactions. E1-L2 forms a thioester with FAT10 in vitro, and this reaction requires the active-site cysteine of E1-L2 and the C-terminal diglycine motif of FAT10. Furthermore, endogenous FAT10 forms a thioester with E1-L2 in cells stimulated with tumor necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma), which induce FAT10 expression. Silencing of E1-L2 expression by RNAi blocks the formation of FAT10 conjugates in cells. Deletion of E1-L2 in mice caused embryonic lethality, suggesting that E1-L2 plays an important role in embryogenesis.