The delicate balance between secreted protein folding and endoplasmic reticulum-associated degradation in human physiology.
The delicate balance between secreted protein folding and endoplasmic reticulum-associated degradation in human physiology.
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DOI：
10.1152/physrev.00027.2011
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发表时间：
2012-04
影响因子：
33.6
通讯作者：
Brodsky JL
中科院分区：
文献类型：
--
作者：
Guerriero CJ;Brodsky JL
蛋白质折叠是一个复杂的，容易出错的过程，通常会导致不可修复的蛋白质副产物。这些副产物可以被细胞质量控制机制识别，并被靶向用于蛋白酶体依赖性降解。分泌途径中蛋白质的折叠为蛋白质折叠“问题”增加了另一层，因为内质网在细胞内维持着独特的化学环境。事实上，越来越多的疾病归因于分泌性蛋白质折叠的缺陷，并且这些副产物中的许多被称为内质网相关降解（ERAD）的过程靶向。自其发现以来，对ERAD途径潜在机制的研究为ERAD在正常和疾病状态下如何促进人类健康提供了新的见解。ERAD和疾病之间的联系可以从以下方面得到证明：由于降解而导致的蛋白质功能丧失、当ERAD未能跟上错误折叠的蛋白质产生时的慢性细胞应激、以及一些病原体对ERAD途径的选择能力。越来越多的ERAD底物也阐明了用于识别和降解该途径的大量潜在客户的机制的差异。尽管对ERAD了解很多，但仍存在许多问题，新的范例可能会出现。显然，成功治疗疾病的关键在于确定ERAD途径的分子细节，并了解这种保守途径如何选择和降解无数的底物。
Protein folding is a complex, error-prone process that often results in an irreparable protein by-product. These by-products can be recognized by cellular quality control machineries and targeted for proteasome-dependent degradation. The folding of proteins in the secretory pathway adds another layer to the protein folding “problem,” as the endoplasmic reticulum maintains a unique chemical environment within the cell. In fact, a growing number of diseases are attributed to defects in secretory protein folding, and many of these by-products are targeted for a process known as endoplasmic reticulum-associated degradation (ERAD). Since its discovery, research on the mechanisms underlying the ERAD pathway has provided new insights into how ERAD contributes to human health during both normal and diseases states. Links between ERAD and disease are evidenced from the loss of protein function as a result of degradation, chronic cellular stress when ERAD fails to keep up with misfolded protein production, and the ability of some pathogens to coopt the ERAD pathway. The growing number of ERAD substrates has also illuminated the differences in the machineries used to recognize and degrade a vast array of potential clients for this pathway. Despite all that is known about ERAD, many questions remain, and new paradigms will likely emerge. Clearly, the key to successful disease treatment lies within defining the molecular details of the ERAD pathway and in understanding how this conserved pathway selects and degrades an innumerable cast of substrates.
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影响因子：
3.2
作者：
Araki, E;Oyadomari, S;Mori, M
通讯作者：
Mori, M
DOI：
10.1006/bbrc.2000.4139
发表时间：
2001-01-19
影响因子：
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DOI：
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发表时间：
2004-11-05
影响因子：
3.1
作者：
Allen, JR;Nguyen, LX;Urano, F
通讯作者：
Urano, F
影响因子：
32.4
作者：
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通讯作者：
Cresswell, Peter