How Are Proteins Reduced in the Endoplasmic Reticulum?
How Are Proteins Reduced in the Endoplasmic Reticulum?
复制标题
DOI：
10.1016/j.tibs.2017.10.006
复制
发表时间：
2018-01
影响因子：
13.8
通讯作者：
Bulleid NJ
中科院分区：
文献类型：
--
作者：
Ellgaard L;Sevier CS;Bulleid NJ
内质网（ER）内蛋白质巯基氧化的逆转对于蛋白质折叠、降解、伴侣功能和ER应激反应至关重要。我们对这一进程的理解总体上很差，但已经取得了进展。已经鉴定了进行客户蛋白质的初始还原的酶以及途径中的最终电子供体。最近，已经揭示了胞质溶胶在ER蛋白减少中的作用。然而，还原当量是如何从细胞质转移到ER腔仍然是一个悬而未决的问题。我们在这里回顾为什么蛋白质减少ER，讨论最近的数据催化的步骤，在途径中，并考虑氧化还原稳态内的早期分泌途径的影响。分泌途径中正确的二硫键形成需要二硫键形成和二硫键还原。蛋白质巯基修饰被定位于ER的蛋白质二硫键异构酶（PDI）家族成员逆转。一条通路将胞质溶胶中的硫氧还蛋白还原与ER中的二硫化物还原联系起来。错误折叠的ER蛋白需要在细胞溶质中靶向破坏之前被还原。未折叠蛋白反应（UPR）转换器Ire 1和ATF 6受二硫键形成和还原的调节。蛋白质折叠和UPR的关键调节因子BiP通过非典型氧化还原酶Sil1催化的还原来调节。
The reversal of thiol oxidation in proteins within the endoplasmic reticulum (ER) is crucial for protein folding, degradation, chaperone function, and the ER stress response. Our understanding of this process is generally poor but progress has been made. Enzymes performing the initial reduction of client proteins, as well as the ultimate electron donor in the pathway, have been identified. Most recently, a role for the cytosol in ER protein reduction has been revealed. Nevertheless, how reducing equivalents are transferred from the cytosol to the ER lumen remains an open question. We review here why proteins are reduced in the ER, discuss recent data on catalysis of steps in the pathway, and consider the implications for redox homeostasis within the early secretory pathway. Correct disulfide formation within the secretory pathway requires both disulfide bond formation and disulfide reduction. Protein thiol modification is reversed by protein disulfide isomerase (PDI) family members localized to the ER. A pathway links thioredoxin reduction in the cytosol to disulfide reduction in the ER. Misfolded ER proteins need to be reduced before targeting for destruction in the cytosol. The unfolded protein response (UPR) transducers Ire1 and ATF6 are regulated by disulfide bond formation and reduction. The key regulator of protein folding and the UPR, BiP, is modulated by reduction catalyzed by the non-canonical oxidoreductase Sil1.
登录
查看更多内容
影响因子：
5.3
作者：
Higa, Arisa;Taouji, Said;Chevet, Eric
通讯作者：
Chevet, Eric
影响因子：
7.7
作者：
Huang, Chang-jiang;Lin, Chia-yu;Butler, Peter C.
通讯作者：
Butler, Peter C.
影响因子：
4.8
作者：
Brandes, Nicolas;Reichmann, Dana;Jakob, Ursula
通讯作者：
Jakob, Ursula
DOI：
10.3390/v8090242
发表时间：
2016-08-29
期刊：
Viruses
影响因子：
--
作者：
Dupzyk A;Tsai B
通讯作者：
Tsai B
DOI：
10.1083/jcb.201008090
发表时间：
2011-03-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen X;Tukachinsky H;Huang CH;Jao C;Chu YR;Tang HY;Mueller B;Schulman S;Rapoport TA;Salic A
通讯作者：
Salic A