A redox mechanism underlying nucleolar stress sensing by nucleophosmin

The nucleolus has been recently described as a stress sensor. The nucleoplasmic translocation of nucleolar protein nucleophosmin (NPM1) is a hallmark of nucleolar stress; however, the causes of this translocation and its connection to p53 activation are unclear. Using single live-cell imaging and th...

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Main Authors:	Yang, Kai, Wang, Ming, Zhao, Yuzheng, Sun, Xuxu, Yang, Yi, Li, Xie, Zhou, Aiwu, Chu, Huilin, Zhou, Hu, Xu, Jianrong, Wu, Mian, Yang, Jie, Yi, Jing
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133708/

id	pubmed-5133708
recordtype	oai_dc
spelling	pubmed-51337082016-12-21 A redox mechanism underlying nucleolar stress sensing by nucleophosmin Yang, Kai Wang, Ming Zhao, Yuzheng Sun, Xuxu Yang, Yi Li, Xie Zhou, Aiwu Chu, Huilin Zhou, Hu Xu, Jianrong Wu, Mian Yang, Jie Yi, Jing Article The nucleolus has been recently described as a stress sensor. The nucleoplasmic translocation of nucleolar protein nucleophosmin (NPM1) is a hallmark of nucleolar stress; however, the causes of this translocation and its connection to p53 activation are unclear. Using single live-cell imaging and the redox biosensors, we demonstrate that nucleolar oxidation is a general response to various cellular stresses. During nucleolar oxidation, NPM1 undergoes S-glutathionylation on cysteine 275, which triggers the dissociation of NPM1 from nucleolar nucleic acids. The C275S mutant NPM1, unable to be glutathionylated, remains in the nucleolus under nucleolar stress. Compared with wild-type NPM1 that can disrupt the p53–HDM2 interaction, the C275S mutant greatly compromises the activation of p53, highlighting that nucleoplasmic translocation of NPM1 is a prerequisite for stress-induced activation of p53. This study elucidates a redox mechanism for the nucleolar stress sensing and may help the development of therapeutic strategies. Nature Publishing Group 2016-11-25 /pmc/articles/PMC5133708/ /pubmed/27886181 http://dx.doi.org/10.1038/ncomms13599 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yang, Kai Wang, Ming Zhao, Yuzheng Sun, Xuxu Yang, Yi Li, Xie Zhou, Aiwu Chu, Huilin Zhou, Hu Xu, Jianrong Wu, Mian Yang, Jie Yi, Jing
spellingShingle	Yang, Kai Wang, Ming Zhao, Yuzheng Sun, Xuxu Yang, Yi Li, Xie Zhou, Aiwu Chu, Huilin Zhou, Hu Xu, Jianrong Wu, Mian Yang, Jie Yi, Jing A redox mechanism underlying nucleolar stress sensing by nucleophosmin
author_facet	Yang, Kai Wang, Ming Zhao, Yuzheng Sun, Xuxu Yang, Yi Li, Xie Zhou, Aiwu Chu, Huilin Zhou, Hu Xu, Jianrong Wu, Mian Yang, Jie Yi, Jing
author_sort	Yang, Kai
title	A redox mechanism underlying nucleolar stress sensing by nucleophosmin
title_short	A redox mechanism underlying nucleolar stress sensing by nucleophosmin
title_full	A redox mechanism underlying nucleolar stress sensing by nucleophosmin
title_fullStr	A redox mechanism underlying nucleolar stress sensing by nucleophosmin
title_full_unstemmed	A redox mechanism underlying nucleolar stress sensing by nucleophosmin
title_sort	redox mechanism underlying nucleolar stress sensing by nucleophosmin
description	The nucleolus has been recently described as a stress sensor. The nucleoplasmic translocation of nucleolar protein nucleophosmin (NPM1) is a hallmark of nucleolar stress; however, the causes of this translocation and its connection to p53 activation are unclear. Using single live-cell imaging and the redox biosensors, we demonstrate that nucleolar oxidation is a general response to various cellular stresses. During nucleolar oxidation, NPM1 undergoes S-glutathionylation on cysteine 275, which triggers the dissociation of NPM1 from nucleolar nucleic acids. The C275S mutant NPM1, unable to be glutathionylated, remains in the nucleolus under nucleolar stress. Compared with wild-type NPM1 that can disrupt the p53–HDM2 interaction, the C275S mutant greatly compromises the activation of p53, highlighting that nucleoplasmic translocation of NPM1 is a prerequisite for stress-induced activation of p53. This study elucidates a redox mechanism for the nucleolar stress sensing and may help the development of therapeutic strategies.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133708/
_version_	1613752827498201088

A redox mechanism underlying nucleolar stress sensing by nucleophosmin

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