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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Authors | Y Ci, K Shi, J An, Y Yang, K Hui, P Wu, L Shi, C Xu |
Journal | Cell death & disease
(Cell Death Dis)
Vol. 5
Pg. e1542
(Nov 27 2014)
ISSN: 2041-4889 [Electronic] England |
PMID | 25429619
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Intracellular Signaling Peptides and Proteins
- Reactive Oxygen Species
- Tumor Suppressor Protein p53
- Phosphoserine
- Autophagy-Related Protein-1 Homolog
- Protein Serine-Threonine Kinases
- Ribosomal Protein S6 Kinases, 70-kDa
- ULK1 protein, human
- Selenious Acid
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Topics |
- Animals
- Apoptosis
(drug effects)
- Autophagy
(drug effects)
- Autophagy-Related Protein-1 Homolog
- Cell Line, Tumor
- Down-Regulation
(drug effects)
- Humans
- Intracellular Signaling Peptides and Proteins
(metabolism)
- Mice
- Models, Biological
- Phosphorylation
(drug effects)
- Phosphoserine
(metabolism)
- Protein Serine-Threonine Kinases
(metabolism)
- Reactive Oxygen Species
(metabolism)
- Ribosomal Protein S6 Kinases, 70-kDa
(metabolism)
- Selenious Acid
(pharmacology)
- Signal Transduction
(drug effects)
- Tumor Suppressor Protein p53
(metabolism)
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