Host cell sumoylation level influences papillomavirus E2 protein stability.
Host cell sumoylation level influences papillomavirus E2 protein stability.
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DOI：
10.1016/j.virol.2009.02.002
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发表时间：
2009-04-25
期刊：
影响因子：
3.7
通讯作者：
Wilson, Van G.
中科院分区：
文献类型：
--
作者：
Wu, Yu-Chieh;Bian, Xue-Lin;Heaton, Phillip R.;Deyrieux, Adeline F.;Wilson, Van G.
乳头瘤病毒E2蛋白的稳定性受蛋白酶体降解的调节，降解的调节可能有助于在分化皮肤的基底上层中观察到较高的E2蛋白表达水平。我们最近发现E2蛋白被summoylation修饰[Virol 378:329-338]，并且summoylation水平在角化细胞分化过程中上调[J Cell Sci 120:125-136]。这些观察结果，再加上sumoylation已知的防止蛋白酶体降解某些蛋白质的能力，表明这种修饰可能有助于稳定基底上角质形成细胞中的E2蛋白。研究发现，增加总体聚合化的条件会增加细胞内HPV11、16和18 E2蛋白的数量。sumo化对E2转录本没有影响，E2蛋白水平的增加是由于E2蛋白的半衰期大大延长。体外研究证实，sumoylation可以阻断16E2蛋白的蛋白酶体降解。有趣的是，这种稳定作用是间接的，因为它不需要16e2本身的sumoylation，而必须通过细胞靶标的sumoylation起作用。这种依赖于聚合的E2蛋白的间接稳定是一种新的过程，可能将E2水平与细胞环境的变化结合起来。具体来说，我们的研究结果表明，在分化的角质形成细胞中，乳头瘤病毒E2蛋白的水平可能会上调，以响应伴随分化的整体聚合化的增加。
The stability of papillomavirus E2 proteins is regulated by proteasomal degradation, and regulation of degradation could contribute to the higher expression levels E2 proteins observed in suprabasal layers of differentiated skin. We have recently shown that the E2 proteins are modified by sumoylation [ Virol 378:329–338], and that sumoylation levels are up-regulated during keratinocyte differentiation [ J Cell Sci 120:125–136]. These observations, coupled with the known ability of sumoylation to prevent proteasomal degradation of certain proteins, suggested that this modification might contribute to stabilizing E2 proteins in suprabasal keratinocytes. Conditions that increased overall sumoylation were found to increase the intracellular amounts of the HPV11, 16, and 18 E2 proteins. No effect of sumoylation was seen on E2 transcripts, and the increased levels of E2 proteins resulted from a greatly increased half-life for the E2 proteins. In vitro studies confirmed that sumoylation could block the proteasomal degradation of the 16E2 protein. Interestingly, this stabilization effect was indirect as it did not require sumoylation of 16 E2 itself and must be acting through sumoylation of a cellular target(s). This sumoylation-dependent, indirect stabilization of E2 proteins is a novel process that may couple E2 levels to changes in the cellular environment. Specifically, our results suggest that the levels of papillomavirus E2 protein could be upregulated in differentiating keratinocytes in response to the increased overall sumoylation that accompanies differentiation.
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