在亚硒酸盐处理的NB4细胞中，活性氧通过下调由p53磷酸化介导的ULK1来抑制自噬。
ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells.
作者信息
Ci Y, Shi K, An J, Yang Y, Hui K, Wu P, Shi L, Xu C
机构信息
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
出版信息
Cell Death Dis. 2014 Nov 27;5(11):e1542. doi: 10.1038/cddis.2014.506.
Reactive oxygen species (ROS) have an important role in regulating various cellular processes. Our previous study confirmed that selenite, an anti-tumour agent, triggered apoptosis through the production of ROS in multiple types of cancer cells. In this study, we discovered that ROS also inhibited protective autophagy by decreasing the expression of ULK1, an initiator of autophagy, in selenite-treated NB4 cells. Further experiments demonstrated that p-p53 (S392), a phosphorylation event promoted by p70S6K, bound to the promoter of ULK1 and modulated its expression. Experiments in a mouse tumour model with NB4 cells provided in vivo confirmation of the alterations in the p70S6K/p53/ULK1 axis. Collectively, our results show that ROS inhibited autophagy by downregulating the p70S6K/p53/ULK1 axis in selenite-treated NB4 cells.
活性氧（ROS）在调节各种细胞过程中发挥着重要作用。我们之前的研究证实，亚硒酸盐作为一种抗肿瘤剂，通过在多种癌细胞中产生ROS触发细胞凋亡。在本研究中，我们发现ROS还通过降低自噬起始因子ULK1在亚硒酸盐处理的NB4细胞中的表达来抑制保护性自噬。进一步的实验表明，由p70S6K促进的磷酸化事件p-p53（S392）与ULK1的启动子结合并调节其表达。在携带NB4细胞的小鼠肿瘤模型中的实验为p70S6K/p53/ULK1轴的改变提供了体内证实。总体而言，我们的结果表明，ROS通过下调亚硒酸盐处理的NB4细胞中的p70S6K/p53/ULK1轴来抑制自噬。
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