Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation.
Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation.
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DERLIN-2和DERLIN-3受哺乳动物展开的蛋白质反应调节，是ER相关降解所必需的。
DOI：
10.1083/jcb.200507057
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发表时间：
2006-01-30
影响因子：
7.8
通讯作者：
Mori, Kazutoshi
中科院分区：
文献类型：
--
作者：
Oda, Yukako;Okada, Tetsuya;Yoshida, Hiderou;Kaufman, Randal J;Nagata, Kazuhiro;Mori, Kazutoshi
在内质网（ER）中未折叠或错误折叠的蛋白质必须重新折叠或降解以维持ER的稳态。生产性折叠和ER相关降解（ERAD）机制的组成部分已知由未折叠蛋白反应（UPR）上调。我们描述了哺乳动物ERAD，Derlin-2和-3，这表明弱同源性Der 1 p，一个跨膜蛋白参与酵母ERAD的两个新的组件。Derlin-2和Derlin-3均被UPR上调，并且至少Derlin-2是该应答的IRE 1分支的靶标，已知其上调ER降解增强α-甘露糖苷酶样蛋白（EDEM）和EDEM 2（错误折叠糖蛋白的受体样分子）。Derlin-2或-3的过表达加速了错误折叠的糖蛋白的降解，而它们的敲低阻止了降解。Derlin-2和-3与EDEM和p97相关，p97是一种负责提取ERAD底物的胞质ATP酶。这些发现表明，Derlin-2和-3在降解错误折叠的糖蛋白的过程中提供了EDEM和p97之间缺失的环节。
Proteins that are unfolded or misfolded in the endoplasmic reticulum (ER) must be refolded or degraded to maintain the homeostasis of the ER. Components of both productive folding and ER-associated degradation (ERAD) mechanisms are known to be up-regulated by the unfolded protein response (UPR). We describe two novel components of mammalian ERAD, Derlin-2 and -3, which show weak homology to Der1p, a transmembrane protein involved in yeast ERAD. Both Derlin-2 and -3 are up-regulated by the UPR, and at least Derlin-2 is a target of the IRE1 branch of the response, which is known to up-regulate ER degradation enhancing α-mannosidase–like protein (EDEM) and EDEM2, receptor-like molecules for misfolded glycoprotein. Overexpression of Derlin-2 or -3 accelerated degradation of misfolded glycoprotein, whereas their knockdown blocked degradation. Derlin-2 and -3 are associated with EDEM and p97, a cytosolic ATPase responsible for extraction of ERAD substrates. These findings indicate that Derlin-2 and -3 provide the missing link between EDEM and p97 in the process of degrading misfolded glycoproteins.