The E2 Ubiquitin-conjugating Enzymes Direct Polyubiquitination to Preferred Lysines
The E2 Ubiquitin-conjugating Enzymes Direct Polyubiquitination to Preferred Lysines
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DOI：
10.1074/jbc.m109.089003
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发表时间：
2010-03-19
影响因子：
4.8
通讯作者：
Navon, Ami
中科院分区：
文献类型：
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作者：
David, Yael;Ziv, Tamar;Navon, Ami
遍在蛋白-蛋白酶体途径通过降解由多聚遍在蛋白链标记的底物（主要通过遍在蛋白的赖氨酸48连接）在许多细胞过程中发挥着至关重要的作用。虽然泛素通过其其他六个赖氨酸残基的聚合存在于体内作为各种生理途径的一部分，决定多聚泛素链类型的分子机制在很大程度上仍然未知。我们采取了一个系统的，在体外，方法来评估E2酶的作用，在确定拓扑结构的聚泛素。因为这项研究是在没有E3酶的情况下进行的，我们的数据表明，E2酶能够将泛素化过程导向不同的泛素赖氨酸亚群，这取决于所使用的特定E2。此外，我们的研究结果是在完全一致的赖氨酸优先分配给某些E2在E3的上下文中（在体外和体内）先前的分析。最后，我们的研究结果支持了E2的功能单位是二聚体的观点。据我们所知，这是第一个系统的迹象，参与E2酶在指定聚泛素链组装。
The ubiquitin-proteasome pathway plays a crucial role in many cellular processes by degrading substrates tagged by polyubiquitin chains, linked mostly through lysine 48 of ubiquitin. Although polymerization of ubiquitin via its six other lysine residues exists in vivo as part of various physiological pathways, the molecular mechanisms that determine the type of polyubiquitin chains remained largely unknown. We under took a systematic, in vitro, approach to evaluate the role of E2 enzymes in determining the topology of polyubiquitin. Because this study was performed in the absence of an E3 enzyme, our data indicate that the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines, depending on the specific E2 utilized. Moreover, our findings are in complete agreement with prior analyses of lysine preference assigned to certain E2s in the context of E3 (in vitro and in vivo). Finally, our findings support the rising notion that the functional unit of E2 is a dimer. To our knowledge, this is the first systematic indication for the involvement of E2 enzymes in specifying polyubiquitin chain assembly.