Division of Medical Biotechnology, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
Virus Genes. 2022 Apr;58(2):88-97. doi: 10.1007/s11262-022-01887-8. Epub 2022 Feb 7.
Activating transcription factor 3 (ATF3) is the first p53 stability regulator that interferes with the ubiquitination of p53. However, the E6 oncoprotein of high-risk human papillomaviruses (HPVs) binds to and induces proteasome-dependent degradation of the host p53 protein. Herein, we investigate the effects of ATF3 overexpression on cell cycle progression and apoptosis in HPV-18-infected HeLa cells, and further examine whether ATF3 could alter the apoptosis level of HeLa cells through the inhibition of E6-mediated p53 degradation. Cytological function of HeLa cells prior and subsequent to the overexpression of ATF3 was assessed using cell cycle and annexin V/PI flow cytometry analysis. Western blotting assays revealed no significant effect of ATF3 on the levels of p53 and E6 in HeLa cells. However, annexin V staining demonstrated increases in apoptosis. ATF3 acts as a tumor suppressor factor in HPV18-related cervical cancer which mediates apoptotic functions through a p53-independent pathway.
激活转录因子 3（ATF3）是第一个干扰 p53 泛素化的 p53 稳定性调节剂。然而，高危型人乳头瘤病毒（HPV）的 E6 癌蛋白与宿主 p53 蛋白结合，并诱导其蛋白酶体依赖性降解。在此，我们研究了 ATF3 过表达对 HPV-18 感染的 HeLa 细胞细胞周期进程和凋亡的影响，并进一步探讨 ATF3 是否可以通过抑制 E6 介导的 p53 降解来改变 HeLa 细胞的凋亡水平。通过细胞周期和 Annexin V/PI 流式细胞术分析评估了 HeLa 细胞在过表达 ATF3 前后的细胞学功能。Western blot 分析显示，ATF3 对 HeLa 细胞中 p53 和 E6 的水平没有显著影响。然而，Annexin V 染色显示凋亡增加。ATF3 作为 HPV18 相关宫颈癌的肿瘤抑制因子，通过 p53 非依赖性途径介导凋亡功能。
