A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly
A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly
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DOI：
10.1016/s0092-8674(00)80574-7
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发表时间：
1999-03-05
期刊：
影响因子：
64.5
通讯作者：
Jentsch, S
中科院分区：
文献类型：
--
作者：
Koegl, M;Hoppe, T;Jentsch, S
被多泛素链修饰的蛋白质是蛋白酶体的首选底物。泛素化包括一个泛素激活酶E1，一个泛素结合酶E2，通常还有一个底物特异性泛素蛋白连接酶E3。本研究表明，蛋白酶体靶向模型底物所需的高效多泛素化需要一个额外的偶联因子，称为E4。这种蛋白，以前在酵母中被称为UFD2，与预先形成的偶联物的泛素部分结合，并催化泛素链与E1， E2和E3结合。有趣的是，E4定义了一个新的蛋白质家族，包括两个人类成员和来自盘基骨菌的子实体发育所需的调节蛋白NOSA。在酵母中，E4活性与应激条件下的细胞存活有关，这表明真核生物利用E4依赖性蛋白水解途径实现多种细胞功能。
Proteins modified by multiubiquitin chains are the preferred substrates of the proteasome. Ubiquitination involves a ubiquitin-activating enzyme, E1, a ubiquitin-conjugating enzyme, E2, and often a substrate-specific ubiquitin-protein ligase, E3. Here we show that efficient multiubiquitination needed for proteasomal targeting of a model substrate requires an additional conjugation factor, named E4. This protein, previously known as UFD2 in yeast, binds to the ubiquitin moieties of preformed conjugates and catalyzes ubiquitin chain assembly in conjunction with E1, E2, and E3. Intriguingly, E4 defines a novel protein family that includes two human members and the regulatory protein NOSA from Dictyostelium required for fruiting body development. In yeast, E4 activity is linked to cell survival under stress conditions, indicating that eukaryotes utilize E4-dependent proteolysis pathways for multiple cellular functions.