Prabhu N S, Somasundaram K, Satyamoorthy K, Herlyn M, El-Deiry W S
Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148, USA.
Int J Oncol. 1998 Jul;13(1):5-9. doi: 10.3892/ijo.13.1.5.
Human papillomavirus (HPV) is the major cause of cervical cancer worldwide. HPV-E6 protein targets the p53 tumor suppressor protein for degradation by ubiquitin-mediated proteolysis making such cancers resistant to p53-gene therapy. Here we show that infection of human cancer cells by E6-expressing adenovirus (Ad-E6) leads to degradation of both wild-type or mutant p53 protein. Interestingly, the p53-homologue candidate tumor suppressor p73 is not degraded in Ad-E6 infected cancer cells. Wild-type p73beta and not wild-type p53 or mutant p73 is a potent inhibitor of cancer colony growth and inducer of apoptosis, despite HPV-E6 overexpression. The results suggest a novel strategy using p73beta in gene therapy of HPV-E6 expressing cancers.
人乳头瘤病毒（HPV）是全球宫颈癌的主要病因。HPV-E6蛋白通过泛素介导的蛋白水解作用靶向降解p53肿瘤抑制蛋白，使得此类癌症对p53基因治疗产生抗性。在此我们表明，表达E6的腺病毒（Ad-E6）感染人类癌细胞会导致野生型或突变型p53蛋白降解。有趣的是，p53同源候选肿瘤抑制因子p73在Ad-E6感染的癌细胞中不会降解。尽管HPV-E6过表达，但野生型p73β而非野生型p53或突变型p73是癌症集落生长的有效抑制剂和凋亡诱导剂。这些结果提示了一种在HPV-E6表达癌症的基因治疗中使用p73β的新策略。
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