气候变化领域集成服务门户(CCPortal): p62-containing, proteolytically active nuclear condensates, increase the efficiency of the ubiquitin-proteasome system

CCPortal

DOI	10.1073/pnas.2107321118
	p62-containing, proteolytically active nuclear condensates, increase the efficiency of the ubiquitin-proteasome system
	Fu A.; Cohen-Kaplan V.; Avni N.; Livneh I.; Ciechanover A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:33
英文摘要	Degradation of a protein by the ubiquitin-proteasome system (UPS) is a multistep process catalyzed by sequential reactions. Initially, ubiquitin is conjugated to the substrate in a process mediated by concerted activity of three enzymes; the last of them-a ubiquitin ligase (E3)-belongs to a family of several hundred members, each recognizing a few specific substrates. This is followed by repeated addition of ubiquitin moieties to the previously conjugated one to generate a ubiquitin chain that serves as a recognition element for the proteasome, which then degrades the substrate. Ubiquitin is recycled via the activity of deubiquitinating enzymes (DUBs). It stands to reason that efficiency of such a complex process would depend on colocalization of the different components in an assembly that allows the reactions to be carried out sequentially and processively. Here we describe nuclear condensates that are dynamic in their composition. They contain p62 as an essential component. These assemblies are generated by liquid-liquid phase separation (LLPS) and also contain ubiquitinated targets, 26S proteasome, the three conjugating enzymes, and DUBs. Under basal conditions, they serve as efficient centers for proteolysis of nuclear proteins (e.g., c-Myc) and unassembled subunits of the proteasome, suggesting they are involved in cellular protein quality control. Supporting this notion is the finding that such foci are also involved in degradation of misfolded proteins induced by heat and oxidative stresses, following recruitment of heat shock proteins and their associated ubiquitin ligase CHIP. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	LLPS condensates; P62; Proteasome; Protein degradation; Ubiquitin
语种	英语
scopus关键词	deubiquitinase; heat shock protein; Myc protein; nuclear protein; proteasome; sequestosome 1; P62 protein, human; proteasome; RNA binding protein; ubiquitin; A-549 cell line; Article; cell damage; cell nucleus; controlled study; heat stress; HeLa cell line; MCF-7 cell line; MDA-MB-231 cell line; nuclear export signal; nuclear localization signal; oxidative stress; phase separation; protein assembly; protein degradation; protein misfolding; protein unfolding; ubiquitin proteasome system; ubiquitination; gene deletion; gene expression regulation; genetics; heat; human; metabolism; osmotic pressure; physiological stress; physiology; Gene Deletion; Gene Expression Regulation; HeLa Cells; Hot Temperature; Humans; Osmotic Pressure; Oxidative Stress; Proteasome Endopeptidase Complex; RNA-Binding Proteins; Stress, Physiological; Ubiquitin
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/251056
作者单位	Technion Rappaport Integrated Cancer Center, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, 3109601, Israel
推荐引用方式 GB/T 7714	Fu A.,Cohen-Kaplan V.,Avni N.,et al. p62-containing, proteolytically active nuclear condensates, increase the efficiency of the ubiquitin-proteasome system[J],2021,118(33).
APA	Fu A.,Cohen-Kaplan V.,Avni N.,Livneh I.,&Ciechanover A..(2021).p62-containing, proteolytically active nuclear condensates, increase the efficiency of the ubiquitin-proteasome system.Proceedings of the National Academy of Sciences of the United States of America,118(33).
MLA	Fu A.,et al."p62-containing, proteolytically active nuclear condensates, increase the efficiency of the ubiquitin-proteasome system".Proceedings of the National Academy of Sciences of the United States of America 118.33(2021).