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

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 p...

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Detalles Bibliográficos
Autores principales: Ci, Y, Shi, K, An, J, Yang, Y, Hui, K, Wu, P, Shi, L, Xu, C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260759/
https://www.ncbi.nlm.nih.gov/pubmed/25429619
http://dx.doi.org/10.1038/cddis.2014.506
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author Ci, Y
Shi, K
An, J
Yang, Y
Hui, K
Wu, P
Shi, L
Xu, C
author_facet Ci, Y
Shi, K
An, J
Yang, Y
Hui, K
Wu, P
Shi, L
Xu, C
author_sort Ci, Y
collection PubMed
description 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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spelling pubmed-42607592014-12-15 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 Original Article 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. Nature Publishing Group 2014-11 2014-11-27 /pmc/articles/PMC4260759/ /pubmed/25429619 http://dx.doi.org/10.1038/cddis.2014.506 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0
spellingShingle Original Article
Ci, Y
Shi, K
An, J
Yang, Y
Hui, K
Wu, P
Shi, L
Xu, C
ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells
title ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells
title_full ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells
title_fullStr ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells
title_full_unstemmed ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells
title_short ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells
title_sort ros inhibit autophagy by downregulating ulk1 mediated by the phosphorylation of p53 in selenite-treated nb4 cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260759/
https://www.ncbi.nlm.nih.gov/pubmed/25429619
http://dx.doi.org/10.1038/cddis.2014.506
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