International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste, Italy.
Virology. 2013 Nov;446(1-2):389-96. doi: 10.1016/j.virol.2013.08.016. Epub 2013 Sep 17.
The Human Papillomavirus E6 oncoproteins have the capacity to target several of their cellular interacting partners for proteasome mediated degradation, and recent proteomic analyses suggest a close involvement of E6 with the cellular proteasome machinery. In this study we have performed an extensive analysis of the capacity of different E6 oncoproteins to interact with specific proteasome components. We demonstrate that multiple subunits of the proteasome can be bound by different HPV E6 oncoproteins. Furthermore, whilst most of these interactions appear independent of the E6AP ubiquitin ligase, the association of E6 with the major ubiquitin-accepting proteasome subunit, S5a, does require the presence of E6AP. One consequence of the interaction between E6/E6AP and S5a is enhanced ubiquitination of this proteasome subunit. These results suggest a complex interplay between E6 and the proteasome, only some aspects of which are dependent upon the E6AP ubiquitin ligase.
人乳头瘤病毒 E6 癌蛋白能够靶向其几种细胞相互作用伙伴进行蛋白酶体介导的降解，最近的蛋白质组学分析表明 E6 与细胞蛋白酶体机制密切相关。在这项研究中，我们对不同 E6 癌蛋白与特定蛋白酶体成分相互作用的能力进行了广泛分析。我们证明，蛋白酶体的多个亚基可以被不同的 HPV E6 癌蛋白结合。此外，虽然这些相互作用中的大多数似乎独立于 E6AP 泛素连接酶，但 E6 与主要的泛素接受蛋白酶体亚基 S5a 的关联确实需要 E6AP 的存在。E6/E6AP 和 S5a 之间相互作用的一个后果是增强了该蛋白酶体亚基的泛素化。这些结果表明 E6 与蛋白酶体之间存在复杂的相互作用，其中只有某些方面依赖于 E6AP 泛素连接酶。
