HPV E6 proteins target Ubc9, the SUMO conjugating enzyme.
HPV E6 proteins target Ubc9, the SUMO conjugating enzyme.
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DOI：
10.1016/j.virusres.2011.04.001
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发表时间：
2011-06
期刊：
影响因子：
5
通讯作者：
Wilson, Van G.
中科院分区：
文献类型：
--
作者：
Heaton, Phillip R.;Deyrieux, Adeline F.;Bian, Xue-Lin;Wilson, Van G.
人乳头瘤病毒致癌蛋白E6与许多细胞蛋白相互作用，对于某些靶点，E6通过泛素-蛋白酶体途径指导其降解。泛素样修饰物（如SUMO）的翻译后修饰也影响蛋白质活性、蛋白质-蛋白质相互作用和蛋白质稳定性。我们报告说，高风险的HPVE6蛋白减少细胞内的数量的唯一SUMO结合酶，Ubc9，伴随着主机sumoylation减少。E6对Ubc9的转录没有显著影响，表明这种影响可能是在蛋白质水平上。与典型的E6介导的蛋白酶体降解一致，E6在体外与Ubc9结合，并且需要E6AP来降低Ubc9水平。在分化的角质形成细胞中，在稳定的E6表达条件下，Ubc9减少，并且许多sumoylated靶点丢失，这表明正常的sumoylation谱的显著扰动。虽然已知E6抑制PIASy（一种SUMO连接酶），但我们的研究结果表明HPV E6还靶向Ubc9蛋白以调节宿主细胞SUMO化，这表明SUMO化系统可能是病毒繁殖过程中的重要靶点，并可能是宫颈癌后续发展的重要靶点。
The human papillomavirus oncogenic protein, E6, interacts with a number of cellular proteins, and for some targets, E6 directs their degradation through the ubiquitin-proteasome pathway. Post-translational modification with ubiquitin-like modifiers, such as SUMO, also influences protein activities, protein-protein interactions, and protein stability. We report that the high risk HPVE6 proteins reduce the intracellular quantity of the sole SUMO conjugation enzyme, Ubc9, concomitant with decreased host sumoylation. E6 did not significantly influence transcription of Ubc9, indicating that the effects were likely at the protein level. Consistent with typical E6-mediated proteasomal degradation, E6 bound to Ubc9 in vitro, and required E6AP for reduction of Ubc9 levels. Under stable E6 expression conditions in differentiating keratinocytes there was a decrease in Ubc9 and a loss of numerous sumoylated targets indicating a significant perturbation of the normal sumoylation profile. While E6 is known to inhibit PIASy, a SUMO ligase, our results suggest that HPV E6 also targets the Ubc9 protein to modulate host cell sumoylation, suggesting that the sumoylation system may be an important target during viral reproduction and possibly the subsequent development of cervical cancer.
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DOI：
10.1007/978-90-481-2649-1_18
发表时间：
2009-01-01
期刊：
SUMO REGULATION OF CELLULAR PROCESSES
影响因子：
--
作者：
Deyrieux, Adeline F.;Wilson, Van G.
通讯作者：
Wilson, Van G.
影响因子：
6.7
作者：
Chang TH;Kubota T;Matsuoka M;Jones S;Bradfute SB;Bray M;Ozato K
通讯作者：
Ozato K
影响因子：
16
作者：
Boggio, R;Colombo, R;Chiocca, S
通讯作者：
Chiocca, S
影响因子：
16
作者：
Bischof, Oliver;Schwamborn, Klaus;Dejean, Anne
通讯作者：
Dejean, Anne
影响因子：
8
作者：
Desaintes, C;Goyat, S;Thierry, F
通讯作者：
Thierry, F