Vembar Shruthi S, Brodsky Jeffrey L
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Nat Rev Mol Cell Biol. 2008 Dec;9(12):944-57. doi: 10.1038/nrm2546. Epub 2008 Nov 12.
Protein folding in the endoplasmic reticulum (ER) is monitored by ER quality control (ERQC) mechanisms. Proteins that pass ERQC criteria traffic to their final destinations through the secretory pathway, whereas non-native and unassembled subunits of multimeric proteins are degraded by the ER-associated degradation (ERAD) pathway. During ERAD, molecular chaperones and associated factors recognize and target substrates for retrotranslocation to the cytoplasm, where they are degraded by the ubiquitin-proteasome machinery. The discovery of diseases that are associated with ERAD substrates highlights the importance of this pathway. Here, we summarize our current understanding of each step during ERAD, with emphasis on the factors that catalyse distinct activities.
内质网（ER）中的蛋白质折叠由内质网质量控制（ERQC）机制进行监测。通过ERQC标准的蛋白质通过分泌途径转运至其最终目的地，而多聚体蛋白的非天然和未组装亚基则通过内质网相关降解（ERAD）途径被降解。在ERAD过程中，分子伴侣和相关因子识别底物并将其靶向转运回细胞质进行逆向转运，在细胞质中它们被泛素-蛋白酶体机制降解。与ERAD底物相关的疾病的发现凸显了该途径的重要性。在此，我们总结了目前对ERAD过程中每个步骤的理解，重点关注催化不同活性的因子。
