ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells.
ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells.
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DOI：
10.1038/cddis.2014.506
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发表时间：
2014-11-27
影响因子：
9
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活性氧（ROS）在调节各种细胞过程中具有重要作用。我们以前的研究证实，亚硒酸盐，一种抗肿瘤剂，通过在多种类型的癌细胞中产生ROS触发细胞凋亡。在这项研究中，我们发现ROS还通过降低亚硒酸盐处理的NB 4细胞中自噬启动子ULK 1的表达来抑制保护性自噬。进一步的实验表明，p-p53（S392），由p70 S6 K促进的磷酸化事件，结合到ULK 1的启动子，并调节其表达。用NB 4细胞在小鼠肿瘤模型中进行的实验提供了p70 S6 K/p53/ULK 1轴改变的体内确认。总的来说，我们的研究结果表明，ROS通过下调p70 S6 K/p53/ULK 1轴在亚硒酸盐处理的NB 4细胞抑制自噬。
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.