EDEM as an acceptor of terminally misfolded glycoproteins released from calnexin
EDEM as an acceptor of terminally misfolded glycoproteins released from calnexin
复制标题
DOI：
10.1126/science.1079181
复制
发表时间：
2003-02-28
期刊：
影响因子：
56.9
通讯作者：
Nagata, K
中科院分区：
文献类型：
--
作者：
Oda, Y;Hosokawa, N;Nagata, K
内质网（ER）中的末端错误折叠蛋白质被逆向易位到细胞质中，并通过称为ER相关降解（ERAD）的机制被蛋白酶体降解。EDEM是一种假定的Man8B结合蛋白，可加速ER中错误折叠蛋白的降解。在这里，EDEM被证明与钙连接蛋白，但不与钙网蛋白，通过其跨膜区。底物与钙连接蛋白的结合及其从钙连接蛋白中的释放都是ERAD发生所必需的。EDEM的过表达通过促进钙连接蛋白末端错误折叠蛋白的释放来加速ERAD。因此，EDEM似乎通过接受钙连接蛋白的底物在ERAD途径中发挥作用。
Terminally misfolded proteins in the endoplasmic reticulum (ER) are retro-translocated to the cytoplasm and degraded by proteasomes through a mechanism known as ER-associated degradation (ERAD). EDEM, a postulated Man8B-binding protein, accelerates the degradation of misfolded proteins in the ER. Here, EDEM was shown to interact with calnexin, but not with calreticulin, through its transmembrane region. Both binding of substrates to calnexin and their release from calnexin were required for ERAD to occur. Overexpression of EDEM accelerated ERAD by promoting the release of terminally misfolded proteins from calnexin. Thus, EDEM appeared to function in the ERAD pathway by accepting substrates from calnexin.