Institute for Research in Biomedicine, Bellinzona, Switzerland.
Autophagy. 2012 Oct;8(10):1534-6. doi: 10.4161/auto.21229. Epub 2012 Aug 16.
Secretory and membrane proteins attain their native structure in the endoplasmic reticulum (ER). Folding-defective polypeptides are selected for degradation by processes collectively defined as ER-associated degradation (ERAD). Enhanced ERAD activity may interfere with protein biogenesis by inappropriately targeting not-yet-native protein folding intermediates for disposal. The regulation of ERAD is therefore crucial to maintain cellular proteostasis. At steady-state, select ERAD regulators are constitutively removed from the ER in a series of processes collectively defined as ERAD tuning. This sets the ERAD activity at levels that do not interfere with completion of ongoing folding programs. Our latest work highlights a crucial, autophagy-independent role of nonlipidated LC3 (LC3-I) as part of a membrane-bound receptor that insures the vesicle-mediated clearance of at least two ERAD regulators from the ER, EDEM1 and OS9. This pathway is hijacked by coronaviruses (CoV), and silencing of LC3 substantially inhibits viral replication.
分泌蛋白和膜蛋白在内质网（ER）中获得其天然结构。折叠缺陷的多肽通过被统称为 ER 相关降解（ERAD）的过程被选择进行降解。增强的 ERAD 活性可能通过不恰当地将尚未具有天然折叠中间产物靶向处理而干扰蛋白质生物发生。因此，ERAD 的调节对于维持细胞蛋白质稳态至关重要。在稳定状态下，选择的 ERAD 调节剂在一系列统称为 ERAD 调谐的过程中从 ER 中连续不断地被去除。这将 ERAD 活性设定在不干扰正在进行的折叠程序完成的水平。我们的最新工作强调了非脂化 LC3（LC3-I）作为膜结合受体的一部分的关键、自噬非依赖性作用，该受体确保了至少两种 ERAD 调节剂（EDEM1 和 OS9）从 ER 中通过囊泡介导的清除。该途径被冠状病毒（CoV）劫持，并且 LC3 的沉默显著抑制病毒复制。
