Roles for ATF6 and the sarco/endoplasmic reticulum protein quality control system in the heart.
Roles for ATF6 and the sarco/endoplasmic reticulum protein quality control system in the heart.
复制标题
DOI：
10.1016/j.yjmcc.2013.09.018
复制
发表时间：
2014-06
影响因子：
5
通讯作者：
Glembotski, Christopher C.
中科院分区：
文献类型：
--
作者：
Glembotski, Christopher C.
关键词：
心肌细胞的肥大生长是一个高度动态的过程，是心脏生理和病理适应的基础。因此，需要更好地了解心肌细胞肥大的分子基础，以充分了解健康和患病心脏大小变化的原因和功能后果。肥大是由心肌细胞蛋白质的增加驱动的，心肌细胞蛋白质的增加必须通过细胞维持蛋白质质量的能力来平衡，以避免有毒错误折叠蛋白质的适应不良积累。最近的研究表明，内质网（ER），其中，在心肌细胞，包括肌/内质网（SR/ER），是大多数蛋白质合成的网站。因此，位于SR/ER的蛋白质质量控制机制可能是心脏是否适应性地响应肥大性生长刺激的重要决定因素。SR/ER-跨膜蛋白ATF 6作为潜在毒性、错误折叠蛋白积累的第一反应者，发挥关键蛋白质质量控制功能。错误折叠的蛋白质将ATF 6转化为转录因子，其调节基因程序，该基因程序部分负责增强蛋白质质量控制。已经在心脏中研究并显示出适应性的两个ATF 6诱导基因是RCAN 1和Der 13，它们分别编码降低蛋白质折叠需求和增强错误折叠蛋白质降解的蛋白质。因此，ATF 6调节的SR/ER蛋白质质量控制系统对于在生长期间维持蛋白质质量是重要的，使得ATF 6和系统的其他组分成为治疗管理病理性心脏肥大的潜在有吸引力的靶标。这篇文章是题为“蛋白质质量控制，泛素蛋白酶体系统和自噬”的特刊的一部分。
The hypertrophic growth of cardiac myocytes is a highly dynamic process that underlies physiological and pathological adaptation of the heart. Accordingly, a better understanding of the molecular underpinnings of cardiac myocyte hypertrophy is required in order to fully appreciate the causes and functional consequences of the changes in the size of the healthy and diseased heart. Hypertrophy is driven by increases in cardiacmyocyte protein, which must be balanced by cellular ability to maintain protein quality in order to avoid maladaptive accumulation of toxic misfolded proteins. Recent studies have shown that the endoplasmic reticulum (ER), which, in cardiac myocytes, comprises the sarco/endoplasmic reticulum (SR/ER), is the site of most protein synthesis. Thus, the protein quality control machinery located at the SR/ER is likely to be an important determinant of whether the heart responds adaptively to hypertrophic growth stimuli. The SR/ER-transmembrane protein, ATF6, serves a critical protein quality control function as a first responder to the accumulation of potentially toxic, misfolded proteins. Misfolded proteins transform ATF6 into a transcription factor that regulates a gene program that is partly responsible for enhancing protein quality control. Two ATF6-inducible genes that have been studied in the heart and shown to be adaptive are RCAN1 and Derl3, which encode proteins that decrease protein-folding demand, and enhance degradation of misfolded proteins, respectively. Thus, the ATF6-regulated SR/ER protein quality control system is important for maintaining protein quality during growth, making ATF6, and other components of the system, potentially attractive targets for the therapeutic management pathological cardiac hypertrophy. This article is part of a Special Issue entitled “Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy”.
登录
查看更多内容
影响因子：
64.5
作者：
Brodsky JL
通讯作者：
Brodsky JL
影响因子：
33.6
作者：
Guerriero CJ;Brodsky JL
通讯作者：
Brodsky JL
内质网相关降解和新型内质网应激反应基因derlin-3的作用。
影响因子：
20.1
作者：
Belmont PJ;Chen WJ;San Pedro MN;Thuerauf DJ;Gellings Lowe N;Gude N;Hilton B;Wolkowicz R;Sussman MA;Glembotski CC
通讯作者：
Glembotski CC
DOI：
10.1038/nrm3495
发表时间：
2013-01
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
13.6
作者：
Doroudgar S;Glembotski CC
通讯作者：
Glembotski CC