{"title":"Signal integration in the endoplasmic reticulum unfolded protein response","authors":"David Ron, Peter Walter","doi":"10.1038/nrm2199","DOIUrl":null,"url":null,"abstract":"Owing to the toxic potential of unfolded proteins, their accumulation in the endoplasmic reticulum activates a cellular stress response. This unfolded protein response remodels the secretory pathway to accommodate the load of unfolded proteins or, if the burden is insurmountable, promotes cell death to protect the organism. The endoplasmic reticulum (ER) responds to the accumulation of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways — cumulatively called the unfolded protein response (UPR). Together, at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids. The arms of the UPR are integrated to provide a response that remodels the secretory apparatus and aligns cellular physiology to the demands imposed by ER stress.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":81.3000,"publicationDate":"2007-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/nrm2199","citationCount":"5758","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Molecular Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://www.nature.com/articles/nrm2199","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 5758
Abstract
Owing to the toxic potential of unfolded proteins, their accumulation in the endoplasmic reticulum activates a cellular stress response. This unfolded protein response remodels the secretory pathway to accommodate the load of unfolded proteins or, if the burden is insurmountable, promotes cell death to protect the organism. The endoplasmic reticulum (ER) responds to the accumulation of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways — cumulatively called the unfolded protein response (UPR). Together, at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids. The arms of the UPR are integrated to provide a response that remodels the secretory apparatus and aligns cellular physiology to the demands imposed by ER stress.
期刊介绍:
Nature Reviews Molecular Cell Biology is a prestigious journal that aims to be the primary source of reviews and commentaries for the scientific communities it serves. The journal strives to publish articles that are authoritative, accessible, and enriched with easily understandable figures, tables, and other display items. The goal is to provide an unparalleled service to authors, referees, and readers, and the journal works diligently to maximize the usefulness and impact of each article. Nature Reviews Molecular Cell Biology publishes a variety of article types, including Reviews, Perspectives, Comments, and Research Highlights, all of which are relevant to molecular and cell biologists. The journal's broad scope ensures that the articles it publishes reach the widest possible audience.