Nishikawa Shuh-ichi, Brodsky Jeffrey L, Nakatsukasa Kunio
Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya 464-8602.
J Biochem. 2005 May;137(5):551-5. doi: 10.1093/jb/mvi068.
Secreted proteins are synthesized at the endoplasmic reticulum (ER), and a quality control mechanism in the ER is essential to maintain secretory pathway homeostasis. Newly synthesized soluble and integral membrane secreted proteins fold into their native conformations with the aid of ER molecular chaperones before they are transported to post-ER compartments. However, terminally mis-folded proteins may be retained in the ER and degraded by a process called ER-associated degradation (ERAD). Recent studies using yeast have shown that molecular chaperones both in the ER and in the cytosol play key roles during the ERAD of mis-folded proteins. One important role for chaperones during ERAD is to prevent substrate protein aggregation. Substrate selection is another important role for molecular chaperones during ERAD.
分泌蛋白在内质网（ER）中合成，内质网中的质量控制机制对于维持分泌途径的稳态至关重要。新合成的可溶性和整合膜分泌蛋白在被转运到内质网后区室之前，借助内质网分子伴侣折叠成其天然构象。然而，终末错误折叠的蛋白可能会保留在内质网中，并通过一种称为内质网相关降解（ERAD）的过程被降解。最近使用酵母进行的研究表明，内质网和细胞质中的分子伴侣在错误折叠蛋白的内质网相关降解过程中都起着关键作用。伴侣蛋白在内质网相关降解过程中的一个重要作用是防止底物蛋白聚集。底物选择是分子伴侣在内质网相关降解过程中的另一个重要作用。
