Natural substrates of the proteasome and their recognition by the ubiquitin system.
Natural substrates of the proteasome and their recognition by the ubiquitin system.
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蛋白酶体的天然底物及其被泛素系统的识别。
DOI：
10.1007/978-3-642-59414-4_6
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发表时间：
2002
影响因子：
--
通讯作者：
H. Ulrich
中科院分区：
文献类型：
--
作者：
H. Ulrich
26S蛋白酶体的多种天然底物有力地证明了泛素/蛋白酶体系统的多样性和灵活性：同时，泛素依赖的降解途径的数量突显了调节蛋白分解对细胞新陈代谢的重要性。这篇综述论述了我们对管理潜在底物识别和靶向的原则的理解的最新进展。虽然泛素激活和结合的机制已被广泛了解，但通过泛素蛋白连接酶来确定底物专一性仍然是一个活跃的研究领域。已经确定了底物蛋白中的几个保守的降解信号，并且越来越清楚的是，这些信号作为特定的E3组的对接位置，而这些E3又遵循一些明确的识别这些基序的策略。特别是，环指蛋白现在正在成为一种新的、显然广泛存在的泛素连接酶。越来越多的E3的发现无疑将更好地揭示这类酶在结构和机制上的共同原理。与通过泛素连接系统识别底物不同，泛素化的蛋白质是如何被运送到26S蛋白酶体的，人们对此知之甚少。毫无疑问，多泛素链是蛋白酶体识别的主要决定因素，已知许多受体和候选靶向因子，其中一些与蛋白酶体本身有关；然而，尚未解决的问题是交替连接的多泛素链所采用的不同几何结构的重要性，亚细胞间转运的作用，以及伴侣在递送步骤中的参与。最后，对泛素不依赖的、底物特定的靶向机制的分析，例如依赖于AZ的ODC的降解，可能为26S蛋白酶体识别蛋白质的问题提供意想不到的答案。
The multitude of natural substrates of the 26S proteasome demonstrates convincingly the diversity and flexibility of the ubiquitin/proteasome system: at the same time, the number of pathways in which ubiquitin-dependent degradation is involved highlights the importance of regulated proteolysis for cellular metabolism. This review has addressed recent advances in our understanding of the principles that govern the recognition and targeting of potential substrates. While the mechanism of ubiquitin activation and conjugation is largely understood, the determination of substrate specificity by ubiquitin protein ligases remains a field of active research. Several conserved degradation signals within substrate proteins have been identified, and it is becoming increasingly clear that these serve as docking sites for specific sets of E3s, which in turn adhere to a number of well-defined strategies for the recognition of these motifs. In particular, RING finger proteins are now emerging as a new and apparently widespread class of ubiquitin ligases. The discovery of more and more E3s will undoubtedly reveal even better the common principles in architecture and mechanisms of this class of enzymes. In contrast to substrate recognition by the ubiquitin conjugation system, the way in which a ubiquitylated protein is delivered to the 26S proteasome is poorly understood. There is no doubt that multiubiquitin chains serve as the principal determinant for recognition by the proteasome, and a number of receptors and candidate targeting factors are known, some of which are associated with the proteasome itself; however, unresolved issues are the significance of the different geometries that alternatively linked multiubiquitin chains can adopt, the role of transport between subcellular compartments, as well as the participation of chaperones in the delivery step. Finally, the analysis of ubiquitin-independent, substrate-specific targeting mechanisms, such as the AZ-dependent degradation of ODC, may provide unexpected answers to questions about protein recognition by the 26S proteasome.
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影响因子：
10.5
作者：
CohenFix, O;Peters, JM;Koshland, D
通讯作者：
Koshland, D
DOI：
--
发表时间：
1983-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Hershko;H. Heller;S. Elias;A. Ciechanover
通讯作者：
A. Hershko;H. Heller;S. Elias;A. Ciechanover
影响因子：
56.9
作者：
ROGERS, S;WELLS, R;RECHSTEINER, M
通讯作者：
RECHSTEINER, M
DOI：
10.1073/pnas.93.9.4294
发表时间：
1996-04-30
影响因子：
11.1
作者：
Aristarkhov, A;Eytan, E;Ruderman, JV
通讯作者：
Ruderman, JV
影响因子：
56.9
作者：
Yang, Y;Fang, SY;Ashwell, JD
通讯作者：
Ashwell, JD