Substrate-specific mediators of ER associated degradation (ERAD).

Substrate-specific mediators of ER associated degradation (ERAD).
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DOI:
10.1016/j.ceb.2009.04.006
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发表时间:
2009-08
影响因子:
7.5
通讯作者:
Wojcikiewicz RJ
Wojcikiewicz RJ
中科院分区:
生物学2区
文献类型:
--
作者:
Brodsky JL;Wojcikiewicz RJ

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大约三分之一的新合成真核蛋白靶向分泌途径,分泌途径由一个细胞器网络组成,该网络容纳酶并维持分泌蛋白和膜蛋白成熟所需的化学环境。然而,这种多样化的蛋白质组可能无法达到其天然状态,因此被选择进行内质网相关降解(ERAD)。在过去的几年中,已经做出了重大的努力来解剖核心ERAD机制的组成部分,这些组成部分负责大多数ERAD底物的破坏。然而,有趣的是,一些ERAD底物与专用的伴侣样蛋白结合,这些蛋白靶向它们进行蛋白水解或保护它们免受破坏。其他底物折叠和功能正常,但可以被识别和传递调节信号的蛋白质接头选择用于ERAD。
Approximately one-third of newly synthesized eukaryotic proteins are targeted to the secretory pathway, which is composed of an organellar network that houses the enzymes and maintains the chemical environment required for the maturation of secreted and membrane proteins. Nevertheless, this diverse group of proteins may fail to achieve their native states and are consequently selected for ER associated degradation (ERAD). Over the past few years, significant effort has been made to dissect the components of the core ERAD machinery that is responsible for the destruction of most ERAD substrates. Interestingly, however, some ERAD substrates associate with dedicated chaperone-like proteins that target them for proteolysis or protect them from destruction. Other substrates fold and function normally but can be selected for ERAD by protein adaptors that identify and transmit regulatory cues.
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