粒体自噬
自噬
细胞生长
爱泼斯坦-巴尔病毒
活性氧
细胞生物学
癌症研究
端粒酶
生物
化学
病毒
免疫学
细胞凋亡
遗传学
生物化学
基因
作者
Maria Saveria Gilardini Montani,Greta Tarquini,Roberta Santarelli,Roberta Gonnella,Maria Anele Romeo,Rossella Benedetti,Andrea Arena,Alberto Faggioni,Mara Cirone
出处
期刊:Carcinogenesis
[Oxford University Press]
日期:2021-12-27
卷期号:43 (3): 277-287
被引量:7
标识
DOI:10.1093/carcin/bgab116
摘要
Reactive oxygen species (ROS) and DNA repair, respectively, promote and limit oncogenic transformation of B cells driven by Epstein-Barr virus (EBV). We have previously shown that EBV infection reduced autophagy in primary B lymphocytes and enhanced ROS and interleukin 6 (IL-6) release, promoting B-cell proliferation and immortalization. In this study, we explored the role of p62/SQSTM1, accumulated as a consequence of autophagy reduction in EBV-infected B lymphocytes, and found that it exerted a growth-suppressive effect in these cells. At the molecular level, we found that p62 counteracted IL-6 production and ROS increase by interacting with NRF2 and promoting mitophagy. Moreover, p62/NRF2 axis sustained the expression level of H2AX and ataxia-telangiectasia mutated (ATM), whose activation has been shown to have growth-suppressive effects during the first steps of EBV infection, before latency is established. In conclusion, this study shows for the first time that the accumulation of p62 and the activation of p62/axis counteracted EBV-driven proliferation of primary B lymphocytes.
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