Department of Gynecology, First Affiliated Hospital of China Medical University, Shenyang, China.
PLoS One. 2013 Aug 13;8(8):e71453. doi: 10.1371/journal.pone.0071453. eCollection 2013.
High risk subtype HPV16 early oncoprotein E6 contributes host cell immortalization and transformation through interacting with a number of cellular factors. ING4 is one member of the inhibitor of growth (ING) family of type II tumor suppressors and it has been shown to be involved in regulating p53 function. However, the effect and mechanism of HPV16 E6 on ING4 function remain elusive. In this study, we report HPV16 E6 combines with ING4 in vivo and in vitro. The ING4 induced p53 acetylation and its combining with p53 were attenuated by HPV16 E6 independent of p53 degradation. The enhancing function of ING4 on p53 mediated apoptosis was diminished when HPV16 E6 existed. These findings reveal that ING4 may be a common target of oncogenic viruses for driving host cell carcinogenesis.
高危亚型 HPV16 早期癌蛋白 E6 通过与多种细胞因子相互作用，促进宿主细胞永生化和转化。ING4 是生长抑制剂 (ING) 家族的 II 型肿瘤抑制因子的一个成员，它已被证明参与调节 p53 功能。然而，HPV16 E6 对 ING4 功能的影响和机制仍不清楚。在这项研究中，我们报告 HPV16 E6 在体内和体外与 ING4 结合。HPV16 E6 独立于 p53 降解，减弱了 ING4 诱导的 p53 乙酰化及其与 p53 的结合。当存在 HPV16 E6 时，ING4 增强 p53 介导的细胞凋亡的功能减弱。这些发现表明，ING4 可能是致癌病毒的一个共同靶点，用于驱动宿主细胞癌变。
