Ubiquitin-proteasome pathway and cellular responses to oxidative stress.
Ubiquitin-proteasome pathway and cellular responses to oxidative stress.
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DOI：
10.1016/j.freeradbiomed.2011.03.031
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发表时间：
2011-07-01
影响因子：
7.4
通讯作者：
Taylor, Allen
中科院分区：
文献类型：
--
作者：
Shang, Fu;Taylor, Allen
泛素-蛋白酶体途径（UPP）是选择性降解各种形式的受损蛋白的主要胞质蛋白水解机制。因此，UPP是一种重要的蛋白质质量控制机制。在典型的UPP中，泛素和26 S蛋白酶体都参与其中。经典UPP的底物蛋白首先被多个泛素分子标记，然后被26 S蛋白酶体降解。然而，在非经典UPP中，蛋白质可以被26 S或20 S蛋白酶体降解，而不会被遍在蛋白化。很明显，蛋白酶体负责氧化蛋白的选择性降解，但泛素化在这个过程中的参与程度仍然是一个争论的主题。虽然许多出版物表明20 S蛋白酶体降解氧化蛋白不依赖于泛素，但也有确凿的证据表明泛素和泛素化参与某些形式的氧化蛋白的降解。细胞需要一个功能齐全的UPP来科普氧化应激，并且UPP的活性也受到细胞氧化还原状态的调节。轻度或短暂的氧化应激上调细胞和组织中的泛素化系统和蛋白酶体活性，并短暂增强细胞内蛋白水解。严重或持续的氧化应激损害UPP的功能并减少细胞内蛋白水解。泛素结合酶和蛋白酶体都可以被持续的氧化应激灭活，特别是26 S蛋白酶体。泛素缀合酶和26 S蛋白酶体对氧化损伤的不同亲和性导致泛素缀合物在细胞中响应于轻度氧化应激而积累。因此，细胞中泛素缀合物水平的增加似乎是轻度氧化应激的指标。
The ubiquitin-proteasome pathway (UPP) is the primary cytosolic proteolytic machinery for the selective degradation of various forms of damaged proteins. Thus, the UPP is an important protein quality control mechanism. In the canonical UPP, both ubiquitin and the 26S proteasome are involved. Substrate proteins of the canonical UPP are first tagged by multiple ubiquitin molecules and then degraded by the 26S proteasome. However, in non-canonical UPP, proteins can be degraded by the 26S or the 20S proteasome without being ubiquitinated. It is clear that a proteasome is responsible for selective degradation of oxidized proteins, but the extent to which ubiquitination is involved in this process remains a subject of debate. While many publications suggest that the 20S proteasome degrades oxidized proteins independent of ubiquitin, there is also solid evidence indicating that ubiquitin and ubiquitination are involved in degradation of some forms of oxidized proteins. A fully functional UPP is required for cells to cope with oxidative stress and the activity of the UPP is also modulated by cellular redox status. Mild or transient oxidative stress up-regulates the ubiquitination system and proteasome activity in cells and tissues and transiently enhances intracellular proteolysis. Severe or sustained oxidative stress impairs the function of the UPP and decreases intracellular proteolysis. Both the ubiquitin conjugation enzymes and the proteasome can be inactivated by sustained oxidative stress, especially the 26S proteasome. Differential susceptibilities of the ubiquitin conjugation enzymes and the 26S proteasome to oxidative damage lead to an accumulation of ubiquitin conjugates in cells in response to mild oxidative stress. Thus, increased levels of ubiquitin conjugates in cells appear to be an indicator of mild oxidative stress.
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影响因子：
2.9
作者：
Balog, Edward M.;Lockamy, Elizabeth L.;Thomas, David D.;Ferrington, Deborah A.
通讯作者：
Ferrington, Deborah A.
影响因子：
7.4
作者：
Bulteau, AL;Moreau, M;Friguet, B
通讯作者：
Friguet, B
影响因子：
21.3
作者：
Benaroudj, N;Goldberg, AL
通讯作者：
Goldberg, AL
DOI：
10.1196/annals.1402.078
发表时间：
2007-01-01
期刊：
SKELETAL BIOLOGY AND MEDICINE, PT A
影响因子：
--
作者：
Ciechanover, Aaron
通讯作者：
Ciechanover, Aaron
影响因子：
16
作者：
Bennett, EJ;Bence, NF;Kopito, RR
通讯作者：
Kopito, RR