HPV16 E6通过阻碍ING4对p53作用而抑制细胞凋亡的研究  

Human Papillomavirus 16 E6 Suppresses ING4 Role on p53 to Inhibit Cell Apoptosis

作　　者：郭毅[1] 赵楠[1] 李天人[1] 李慧[1] 

机构地区：[1]中国医科大学附属第一医院妇产科,辽宁沈阳110001

出　　处：《微生物学杂志》2014年第3期56-60,共5页Journal of Microbiology

基　　金：国家自然科学基金(81171649);辽宁省自然科学基金(201102267)

摘　　要：通过HPV16 E6干扰ING4对p53作用的实验研究,探讨HPV16 E6新的致癌机制。采用转染及免疫共沉淀实验证明HPV16 E6阻碍ING4和p53结合及其诱导的p53蛋白乙酰化的作用;将表达p53、ING4和p53报告基因与HPV16 E6或其突变体的质粒共转染p53蛋白阴性的SaoS2细胞系,荧光素酶报告基因检测HPV16 E6抑制ING4对p53基因在转录水平的影响;并采用细胞集落形成实验检测HPV16 E6对ING4所诱导p53途径所致细胞凋亡的抑制。HPV16 E6阻碍ING4和p53结合及其诱导的p53蛋白Lys-382的乙酰化;HPV16 E6减弱ING4在转录水平对p53基因的调控,HPV16 E6抑制ING4诱导的p53途径介导的细胞凋亡,且所有这些作用不依赖p53蛋白的降解。HPV16 E6阻碍ING4对p53的作用而抑制细胞凋亡可能是其引起癌变的途径之一。A new carcinogenetic mechanism was investigated through experimental study of HPV16 E6 interfering ING4 to act on p53. Transfection and immuno precipitation were used to prove the role of HPV16 E6 on ING4 binding with p53 and its induced p53 protein acetylation; the p53 protein negative SaoS2 cell line was co infected with the expression gene of p53, ING4, and p53 reporter gene and HPV16 E6 or plasmid of its mutant, luciferase reporter gene was used to test the inhibition of HPV16 E6 on the ING4 to affect the p53 gene transcription level; cell colony formation experiment was used to test HPV16 E6 on ING4 inducing p53 pathway that caused the apoptosis. HPV16 E6 blocked the ING4 binding with p53 and the acetylation of its induced p53 protein Lys 382; HPV16 E6 attenuated ING4 at transcription level on the regulation of p53 gene. HPV16 E6 inhibited ING4 the induced p53 pathway mediated apoptosis, and all of these actions were independent to p53 protein degradation. The action of HPV16 E6 to block ING4 on p53 to inhibit cell apoptosis possibly was one of the pathways that caused canceration.

关 键 词：HPV16 E6 ING4 P53 乙酰化 凋亡 

分 类 号：Q939.93[生物学—微生物学] R466.5[医药卫生—临床医学]