Regulation of the 26S proteasome complex during oxidative stress.
Regulation of the 26S proteasome complex during oxidative stress.
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DOI：
10.1126/scisignal.2001232
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发表时间：
2010-12-07
影响因子：
7.3
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Wang X;Yen J;Kaiser P;Huang L
蛋白酶体在细胞对氧化应激的反应中起着关键作用。在这里，我们使用生化和质谱方法来研究暴露于过氧化氢 (H2O2) 的酵母和哺乳动物细胞的 26S 蛋白酶体的结构变化。氧化应激诱导20S核心颗粒与26S蛋白酶体的19S调节颗粒解离，导致26S蛋白酶体活性丧失和泛素化蛋白积累。 H2O2 引发蛋白酶体相互作用蛋白 Ecm29 与纯化的 19S 颗粒之间的关联增强。酵母细胞中 ECM29 的缺失阻止了 26S 蛋白酶体因氧化应激而解体，并且 ecm29 突变体比野生型细胞对 H2O2 更敏感，这表明 19S 和 20S 颗粒的分离对于细胞从氧化应激中恢复很重要。需要增加游离 20S 核心颗粒的量来降解氧化蛋白质。蛋白酶体的 Ecm29 依赖性解离独立于 Yap1，Yap1 是一种对酵母氧化应激反应至关重要的转录因子，因此可作为针对 H2O2 诱导的应激的平行防御途径。
The proteasome plays a pivotal role in the cellular response to oxidative stress. Here, we used biochemical and mass spectrometric methods to investigate structural changes in the 26S proteasomes from yeast and mammalian cells exposed to hydrogen peroxide (H2O2). Oxidative stress induced the dissociation of the 20S core particle from the 19S regulatory particle of the 26S proteasome, which resulted in loss of the activities of the 26S proteasome and accumulation of ubiquitinated proteins. H2O2 triggered the increased association of the proteasome-interacting protein Ecm29 with the purified 19S particle. Deletion of ECM29 in yeast cells prevented the disassembly of the 26S proteasome in response to oxidative stress, and ecm29 mutants were more sensitive to H2O2 than were wild-type cells, suggesting that separation of the 19S and 20S particles is important for cellular recovery from oxidative stress. The increased amount of free 20S core particles was required to degrade oxidized proteins. The Ecm29-dependent dissociation of the proteasome was independent of Yap1, a transcription factor that is critical for the oxidative stress response in yeast, and thus functions as a parallel defense pathway against H2O2-induced stress.
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影响因子：
4.4
作者：
Fang L;Wang X;Yamoah K;Chen PL;Pan ZQ;Huang L
通讯作者：
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