人乳头瘤病毒58型E6蛋白对p53的作用研究

Study on the interaction of human papillomavirus type58 E6 with p53 protein

目的 研究HPV5 8E6蛋白与p5 3蛋白的作用关系 ,以初步探讨其致癌机理。方法 先通过GST沉降试验和体外降解试验 ,体外研究HPV5 8E6结合降解p5 3蛋白的作用 ,进而将表达质粒导入SAOS 2细胞 ,在细胞内研究HPV5 8E6对p5 3诱导细胞凋亡活性的影响。结果 HPV5 8E6能够有效结合p5 3蛋白并进一步诱导其降解 ,而且在细胞内 ,HPV5 8E6具有抑制p5 3蛋白的诱导凋亡的功能。结论 p5 3蛋白的降解影响其细胞周期调控和诱导凋亡的功能 ,导致细胞发生恶性转化引发子宫颈癌等肿瘤。

Objective To study the interaction of HPV58 E6 with p53 protein and investigation the carcinogenic mechanism of E6 protein. Methods The binding of HPV58 E6 and p53 proteins and the degradation of p53 induced by HPV58 E6 were detected by GST pull-down assay and in vitro degradation assay. We also investigated the influence of HPV58 E6 protein on the biological activity of p53 in SAOS-2 cells. Result HPV58 E6 bound p53 and mediated its ubiquitin-depended proteolysis. It also inhibited p53 induced cell apoptosis. Conclusion Binding to p53 protein and mediating its ubiquitin-depended proteolysis is the function basis of HPV58 E6′s inhibition of p53-induced apoptosis, and all these may contribute to the oncogenic mechanism of HPV58 E6 protein. [