HECT ubiquitin ligases link viral and cellular PPXY motifs to the vacuolar protein-sorting pathway.
HECT ubiquitin ligases link viral and cellular PPXY motifs to the vacuolar protein-sorting pathway.
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DOI：
10.1083/jcb.200408155
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发表时间：
2005-01-03
期刊：
影响因子：
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通讯作者：
Bieniasz PD
中科院分区：
文献类型：
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作者：
Martin-Serrano J;Eastman SW;Chung W;Bieniasz PD
许多包膜病毒利用E类空泡蛋白分选（VPS）途径从细胞中出芽，并使用肽基序招募特定的E类VPS因子。与E6AP COOH末端（HECT）同源的泛素连接酶已被认为是PPXY基序依赖性出芽的辅因子，但确切地说，该家族的哪些成员负责，以及它们如何进入VPS途径尚不清楚。在这里，我们表明，PPXY依赖的病毒出芽是异常敏感的抑制片段来自特定的HECT泛素连接酶，即WWP1和WWP2。我们还表明，WWP1，WWP2，或痒泛素连接酶招聘促进PPXY依赖的病毒体释放，这一功能需要的HECT泛素连接酶结构域是催化活性。最后，我们表明，几种哺乳动物HECT泛素连接酶，包括WWP1，WWP2，和痒招募到E类室诱导的显性负形式的E类VPS ATP酶，VPS4。这些数据表明，特定的HECT遍在蛋白连接酶可以将PPXY基序连接到VPS途径以诱导病毒萌芽。
Many enveloped viruses exploit the class E vacuolar protein-sorting (VPS) pathway to bud from cells, and use peptide motifs to recruit specific class E VPS factors. Homologous to E6AP COOH terminus (HECT) ubiquitin ligases have been implicated as cofactors for PPXY motif–dependent budding, but precisely which members of this family are responsible, and how they access the VPS pathway is unclear. Here, we show that PPXY-dependent viral budding is unusually sensitive to inhibitory fragments derived from specific HECT ubiquitin ligases, namely WWP1 and WWP2. We also show that WWP1, WWP2, or Itch ubiquitin ligase recruitment promotes PPXY-dependent virion release, and that this function requires that the HECT ubiquitin ligase domain be catalytically active. Finally, we show that several mammalian HECT ubiquitin ligases, including WWP1, WWP2, and Itch are recruited to class E compartments induced by dominant negative forms of the class E VPS ATPase, VPS4. These data indicate that specific HECT ubiquitin ligases can link PPXY motifs to the VPS pathway to induce viral budding.