气候变化领域集成服务门户(CCPortal): SIRT7-dependent deacetylation of NPM promotes p53 stabilization following UV-induced genotoxic stress

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DOI	10.1073/pnas.2015339118
	SIRT7-dependent deacetylation of NPM promotes p53 stabilization following UV-induced genotoxic stress
	Ianni A.; Kumari P.; Tarighi S.; Simonet N.G.; Popescu D.; Guenther S.; Hölper S.; Schmidt A.; Smolka C.; Yue S.; Krüger M.; Fiorillo C.; Vaquero A.; Bober E.; Braun T.
发表日期	2021
ISSN	00278424
卷号	118 期号:5
英文摘要	Adaptation to different forms of environmental stress is crucial for maintaining essential cellular functions and survival. The nucleolus plays a decisive role as a signaling hub for coordinating cellular responses to various extrinsic and intrinsic cues. p53 levels are normally kept low in unstressed cells, mainly due to E3 ubiquitin ligase MDM2-mediated degradation. Under stress, nucleophosmin (NPM) relocates from the nucleolus to the nucleoplasm and binds MDM2, thereby preventing degradation of p53 and allowing cell-cycle arrest and DNA repair. Here, we demonstrate that the mammalian sirtuin SIRT7 is an essential component for the regulation of p53 stability during stress responses induced by ultraviolet (UV) irradiation. The catalytic activity of SIRT7 is substantially increased upon UV irradiation through ataxia telangiectasia mutated and Rad3 related (ATR)-mediated phosphorylation, which promotes efficient deacetylation of the SIRT7 target NPM. Deacetylation is required for stress-dependent relocation of NPM into the nucleoplasm and MDM2 binding, thereby preventing ubiquitination and degradation of p53. In the absence of SIRT7, stress-dependent stabilization of p53 is abrogated, both in vitro and in vivo, impairing cellular stress responses. The study uncovers an essential SIRT7-dependent mechanism for stabilization of the tumor suppressor p53 in response to genotoxic stress. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Acetylation; Nucleolus; Nucleophosmin; P53; Sirtuins
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180818
作者单位	Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, 61231, Germany; Chromatin Biology Laboratory, Josep Carreras Leukaemia Research Institute (IJC), Barcelona, 08916, Spain; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Universität zu Köln, Köln, 50931, Germany; Medizin III Kardiologie und Angiologie, Universitätsklinikum Freiburg, Freiburg, 79106, Germany; State International Science & Technology Cooperation Base of Tumor Immunology and Biological Vaccines, Nankai University, Tianjin, 300071, China; Department of Experimental and Clinical Biomedical Sciences “Mario Serio,”, University of Firenze, Firenze, 50139, Italy; German Center for Lung Research (DZL), Giessen, 35392, Germany; Cardiopulmonary Institute, Bad Nauheim, 61231, Germany
推荐引用方式 GB/T 7714	Ianni A.,Kumari P.,Tarighi S.,et al. SIRT7-dependent deacetylation of NPM promotes p53 stabilization following UV-induced genotoxic stress[J],2021,118(5).
APA	Ianni A..,Kumari P..,Tarighi S..,Simonet N.G..,Popescu D..,...&Braun T..(2021).SIRT7-dependent deacetylation of NPM promotes p53 stabilization following UV-induced genotoxic stress.Proceedings of the National Academy of Sciences of the United States of America,118(5).
MLA	Ianni A.,et al."SIRT7-dependent deacetylation of NPM promotes p53 stabilization following UV-induced genotoxic stress".Proceedings of the National Academy of Sciences of the United States of America 118.5(2021).