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ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells.

Ci Y, Shi K, An J, Yang Y, Hui K, Wu P, Shi L, Xu C - Cell Death Dis (2014)

Bottom Line: Our previous study confirmed that selenite, an anti-tumour agent, triggered apoptosis through the production of ROS in multiple types of cancer cells.Further experiments demonstrated that p-p53 (S392), a phosphorylation event promoted by p70S6K, bound to the promoter of ULK1 and modulated its expression.Collectively, our results show that ROS inhibited autophagy by downregulating the p70S6K/p53/ULK1 axis in selenite-treated NB4 cells.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

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Selenite-induced ROS inhibited the activity of p70S6K, which regulated the phosphorylation of p53 at Ser392. p-p53 (Ser392) acted as a transcription factor to promote the expression of ULK1, an initiator of autophagy, and altered the levels of autophagy and apoptosis
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fig7: Selenite-induced ROS inhibited the activity of p70S6K, which regulated the phosphorylation of p53 at Ser392. p-p53 (Ser392) acted as a transcription factor to promote the expression of ULK1, an initiator of autophagy, and altered the levels of autophagy and apoptosis

Mentions: In summary, we showed that selenite treatment resulted in a rapid increase in ROS in NB4 cells and thus induced apoptosis and blocked protective autophagy through the p70S6K/p53/ULK1 pathway (Figure 7). Similar effect was observed in NB4-derived tumour in vivo. Some other molecules may also be involved in this process, and further studies are required to reveal the detailed mechanisms.


ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells.

Ci Y, Shi K, An J, Yang Y, Hui K, Wu P, Shi L, Xu C - Cell Death Dis (2014)

Selenite-induced ROS inhibited the activity of p70S6K, which regulated the phosphorylation of p53 at Ser392. p-p53 (Ser392) acted as a transcription factor to promote the expression of ULK1, an initiator of autophagy, and altered the levels of autophagy and apoptosis
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4260759&req=5

fig7: Selenite-induced ROS inhibited the activity of p70S6K, which regulated the phosphorylation of p53 at Ser392. p-p53 (Ser392) acted as a transcription factor to promote the expression of ULK1, an initiator of autophagy, and altered the levels of autophagy and apoptosis
Mentions: In summary, we showed that selenite treatment resulted in a rapid increase in ROS in NB4 cells and thus induced apoptosis and blocked protective autophagy through the p70S6K/p53/ULK1 pathway (Figure 7). Similar effect was observed in NB4-derived tumour in vivo. Some other molecules may also be involved in this process, and further studies are required to reveal the detailed mechanisms.

Bottom Line: Our previous study confirmed that selenite, an anti-tumour agent, triggered apoptosis through the production of ROS in multiple types of cancer cells.Further experiments demonstrated that p-p53 (S392), a phosphorylation event promoted by p70S6K, bound to the promoter of ULK1 and modulated its expression.Collectively, our results show that ROS inhibited autophagy by downregulating the p70S6K/p53/ULK1 axis in selenite-treated NB4 cells.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus