Brodsky J L, McCracken A A
Department of Biological Sciences, University of Pittsburgh, PA 15260, USA.
Semin Cell Dev Biol. 1999 Oct;10(5):507-13. doi: 10.1006/scdb.1999.0321.
A variety of mutant polypeptides that are associated with human disease are targeted for degradation by an endoplasmic reticulum (ER) quality control system. In addition, physiological signals and viral gene products can target the degradation of several ER resident proteins and secreted proteins passing through the ER. Although the mechanism of protein quality control and the site of degradation were obscure, recent data indicate that degradation requires the cytosolic proteasome. Biochemical and genetic analyses have indicated that both lumenal and integral membrane proteins are selected for proteolysis and exported to the cytosol by a process that in several cases requires ER associated molecular chaperones.
多种与人类疾病相关的突变多肽会被内质网（ER）质量控制系统靶向降解。此外，生理信号和病毒基因产物可靶向降解几种内质网驻留蛋白以及穿过内质网的分泌蛋白。尽管蛋白质质量控制机制和降解位点尚不清楚，但最近的数据表明，降解需要胞质蛋白酶体。生化和遗传分析表明，管腔蛋白和整合膜蛋白都会被选择进行蛋白水解，并通过一个在某些情况下需要内质网相关分子伴侣的过程输出到细胞质中。
