Adenovirus E4orF6 assembles with Cullin5-ElonginB-ElonginC E3 ubiquitin ligase through an HIV/SIV Vif-like BC-box to regulate p53
Adenovirus E4orF6 assembles with Cullin5-ElonginB-ElonginC E3 ubiquitin ligase through an HIV/SIV Vif-like BC-box to regulate p53
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DOI：
10.1096/fj.06-7241com
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发表时间：
2007-06-01
期刊：
影响因子：
4.8
通讯作者：
Yu, Xiao-Fang
中科院分区：
文献类型：
--
作者：
Luo, Kun;Ehrlich, Elana;Yu, Xiao-Fang
腺病毒蛋白E4orf6针对P53的多泛素化和蛋白酶体降解，并已知与Cul5-ElonginB-ElonginC E3泛素连接酶形成复合体。然而，Cul5是否直接导致E4orf6介导的P53降解尚不清楚。通过使用Cul5的显性负性突变体并通过RNA干扰来沉默Cul5的表达，我们现在已经证明了E4orf6介导的p53降解需要Cul5。此外，我们在E4orf6中发现了一个慢病毒Vif样BC盒基序，它在来自多个物种的腺病毒中高度保守。更重要的是，我们已经证明了这个Vif样的BC-box对于E4orf6招募Cul5-ElonginB-ElonginC E3泛素连接酶是必不可少的，也是E4orf6介导的P53降解所必需的。E4orf6选择性地招募Cul5，尽管既没有Cul5-box，细胞底物受体用来招募Cul5，也没有新发现的HCCH锌结合基序，灵长类慢病毒Vif用来招募Cul5。因此，腺病毒E4orf6分子代表了一个新的病毒BC-box蛋白家族，其细胞祖先尚不清楚。腺病毒E4orf6通过HIV/SIV Vif样BC盒与Cullin5-ElonginB-ElonginC E3泛素连接酶组装，调节P53。
The adenovirus protein E4orf6 targets p53 for polyubiquitination and proteasomal degradation and is known to form a complex with the Cul5-ElonginB- ElonginC E3 ubiquitin ligase. However, whether Cul5 is directly responsible for the E4orf6-mediated degradation of p53 remains unclear. By using a dominant-negative mutant of Cul5 and silencing Cul5 expression through RNA interference, we have now demonstrated that E4orf6- mediated p53 degradation requires Cul5. Furthermore, we have identified a lentiviral Vif-like BC-box motif in E4orf6 that is highly conserved among adenoviruses from multiple species. More importantly, we have shown that this Vif-like BC- box is essential for the recruitment of Cul5-ElonginB-ElonginC E3 ubiquitin ligase by E4orf6 and is also required for E4orf6- mediated p53 degradation. E4orf6 selectively recruited Cul5 despite the lack of either a Cul5-box, which is used by cellular substrate receptors to recruit Cul5, or a newly identified HCCH zinc-binding motif, which is used by primate lentiviral Vif to recruit Cul5. Therefore, adenovirus E4orf6 molecules represent a novel family of viral BC- box proteins the cellular ancestor of which is as yet unknown.-Luo, K., Ehrlich, E., Xiao, Z., Zhang, W., Ketner, G., Yu, X-F. Adenovirus E4orf6 assembles with Cullin5-ElonginB-ElonginC E3 ubiquitin ligase through an HIV/SIV Vif-like BC-box to regulate p53.