Herpes simplex virus type 1 immediate-early protein ICP0 and its isolated RING finger domain act as ubiquitin E3 ligases in vitro
Herpes simplex virus type 1 immediate-early protein ICP0 and its isolated RING finger domain act as ubiquitin E3 ligases in vitro
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DOI：
10.1128/jvi.76.2.841-850.2002
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发表时间：
2002-01-01
影响因子：
5.4
通讯作者：
Everett, RD
中科院分区：
文献类型：
--
作者：
Boutell, C;Sadis, S;Everett, RD
泛素化蛋白的蛋白酶体依赖性降解在许多重要的细胞过程中发挥着关键作用。泛素化需要E1泛素激活酶、E2泛素缀合酶，并且常常需要底物特异性泛素蛋白连接酶(E3)。一类 E3 泛素连接酶已被证明含有常见的锌结合环指基序。我们之前已经证明，单纯疱疹病毒 1 型 ICP0（本身是一种环指蛋白）可诱导多种细胞蛋白的蛋白酶体依赖性降解，并诱导体内共定位缀合泛素的积累。我们现在报道，在 E1 和 E2 酶 UbcH5a 和 UbcH6 存在的情况下，全长 ICP0 及其分离的环指结构域均可在体外诱导多聚泛素链的积累。在其他检测中，RING 逗留区域内的突变会消除体外泛素化活性，也会导致 ICP0 活性严重降低。我们得出的结论是，ICP0 有潜力在病毒感染期间充当 E3 泛素连接酶，并靶向特定细胞蛋白以被 26S 蛋白酶体破坏。
Proteasome-dependent degradation of ubiquitinated proteins plays a key role in many important cellular processes. Ubiquitination requires the El ubiquitin activating enzyme, an E2 ubiquitin conjugating enzyme, and frequently a substrate-specific ubiquitin protein ligase (E3). One class of E3 ubiquitin ligases has been shown to contain a common zinc-binding RING finger motif. We have previously shown that herpes simplex virus type 1 ICP0, itself a RING finger protein, induces the proteasome-dependent degradation of several cellular proteins and induces the accumulation of colocalizing conjugated ubiquitin in vivo. We now report that both full-length ICP0 and its isolated RING finger domain induce the accumulation of polyubiquitin chains in vitro in the presence of E1 and the E2 enzymes UbcH5a and UbcH6. Mutations within the RING linger region that abolish the in vitro ubiquitination activity also cause severe reductions in ICP0 activity, in other assays. We conclude that ICP0 has the potential to act as an E3 ubiquitin ligase during viral infection and to target specific cellular proteins for destruction by the 26S proteasome.