肿瘤细胞内质网应激保护:热休克蛋白TRAP1的多方面作用

IF 0.7
Danilo Swann Matassa, Diana Arzeni, M. Landriscina, F. Esposito
{"title":"肿瘤细胞内质网应激保护:热休克蛋白TRAP1的多方面作用","authors":"Danilo Swann Matassa, Diana Arzeni, M. Landriscina, F. Esposito","doi":"10.2478/ersc-2014-0003","DOIUrl":null,"url":null,"abstract":"Abstract TRAP1 is an HSP90 chaperone, upregulated in human cancers and involved in organelles’ homeostasis and tumor cell metabolism. Indeed, TRAP1 is a key regulator of adaptive responses used by highly proliferative tumors to face the metabolic stress induced by increased demand of protein synthesis and hostile environments. Besides well-characterized roles in prevention of mitochondrial permeability transition pore opening and in regulating mitochondrial respiration, TRAP1 is involved in novel regulatory mechanisms: i) the attenuation of global protein synthesis, ii) the co-translational regulation of protein synthesis and ubiquitination of specific client proteins, and iii) the protection from Endoplasmic Reticulum stress. This provides a crucial role to TRAP1 in maintaining cellular homeostasis through protein quality control, by avoiding the accumulation of damaged or misfolded proteins and, likely, facilitating the synthesis of selective cancer-related proteins. Herein, we summarize how these regulatory mechanisms are part of an integrated network, which enables cancer cells to modulate their metabolism and to face, at the same time, oxidative and metabolic stress, oxygen and nutrient deprivation, increased demand of energy production and macromolecule biosynthesis. The possibility to undertake a new strategy to disrupt such networks of integrated control in cancer cells holds great promise for treatment of human malignancies.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"80 1","pages":"40 - 48"},"PeriodicalIF":0.7000,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":"{\"title\":\"ER stress protection in cancer cells: the multifaceted role of the heat shock protein TRAP1\",\"authors\":\"Danilo Swann Matassa, Diana Arzeni, M. Landriscina, F. Esposito\",\"doi\":\"10.2478/ersc-2014-0003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Abstract TRAP1 is an HSP90 chaperone, upregulated in human cancers and involved in organelles’ homeostasis and tumor cell metabolism. Indeed, TRAP1 is a key regulator of adaptive responses used by highly proliferative tumors to face the metabolic stress induced by increased demand of protein synthesis and hostile environments. Besides well-characterized roles in prevention of mitochondrial permeability transition pore opening and in regulating mitochondrial respiration, TRAP1 is involved in novel regulatory mechanisms: i) the attenuation of global protein synthesis, ii) the co-translational regulation of protein synthesis and ubiquitination of specific client proteins, and iii) the protection from Endoplasmic Reticulum stress. This provides a crucial role to TRAP1 in maintaining cellular homeostasis through protein quality control, by avoiding the accumulation of damaged or misfolded proteins and, likely, facilitating the synthesis of selective cancer-related proteins. Herein, we summarize how these regulatory mechanisms are part of an integrated network, which enables cancer cells to modulate their metabolism and to face, at the same time, oxidative and metabolic stress, oxygen and nutrient deprivation, increased demand of energy production and macromolecule biosynthesis. The possibility to undertake a new strategy to disrupt such networks of integrated control in cancer cells holds great promise for treatment of human malignancies.\",\"PeriodicalId\":29730,\"journal\":{\"name\":\"Cell Pathology\",\"volume\":\"80 1\",\"pages\":\"40 - 48\"},\"PeriodicalIF\":0.7000,\"publicationDate\":\"2014-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Pathology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2478/ersc-2014-0003\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Pathology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2478/ersc-2014-0003","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3

摘要

TRAP1是一种HSP90伴侣蛋白,在人类癌症中表达上调,参与细胞器稳态和肿瘤细胞代谢。事实上,TRAP1是高增殖肿瘤面对蛋白质合成需求增加和恶劣环境引起的代谢应激时所使用的适应性反应的关键调节因子。除了在防止线粒体通透性过渡开孔和调节线粒体呼吸方面具有众所周知的作用外,TRAP1还参与了新的调节机制:1)全球蛋白质合成的减弱,2)蛋白质合成和特定客户蛋白泛素化的共翻译调节,以及3)内质网应激的保护。这为TRAP1通过蛋白质质量控制维持细胞稳态提供了关键作用,避免了受损或错误折叠蛋白质的积累,并可能促进了选择性癌症相关蛋白质的合成。在此,我们总结了这些调节机制如何成为一个综合网络的一部分,该网络使癌细胞能够调节其代谢,同时面临氧化和代谢应激,氧气和营养剥夺,能量生产和大分子生物合成需求增加。采取一种新的策略来破坏癌细胞中这种综合控制网络的可能性,为治疗人类恶性肿瘤带来了巨大的希望。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ER stress protection in cancer cells: the multifaceted role of the heat shock protein TRAP1
Abstract TRAP1 is an HSP90 chaperone, upregulated in human cancers and involved in organelles’ homeostasis and tumor cell metabolism. Indeed, TRAP1 is a key regulator of adaptive responses used by highly proliferative tumors to face the metabolic stress induced by increased demand of protein synthesis and hostile environments. Besides well-characterized roles in prevention of mitochondrial permeability transition pore opening and in regulating mitochondrial respiration, TRAP1 is involved in novel regulatory mechanisms: i) the attenuation of global protein synthesis, ii) the co-translational regulation of protein synthesis and ubiquitination of specific client proteins, and iii) the protection from Endoplasmic Reticulum stress. This provides a crucial role to TRAP1 in maintaining cellular homeostasis through protein quality control, by avoiding the accumulation of damaged or misfolded proteins and, likely, facilitating the synthesis of selective cancer-related proteins. Herein, we summarize how these regulatory mechanisms are part of an integrated network, which enables cancer cells to modulate their metabolism and to face, at the same time, oxidative and metabolic stress, oxygen and nutrient deprivation, increased demand of energy production and macromolecule biosynthesis. The possibility to undertake a new strategy to disrupt such networks of integrated control in cancer cells holds great promise for treatment of human malignancies.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信