Caspase activation inhibits proteasome, function during apoptosis
Caspase activation inhibits proteasome, function during apoptosis
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DOI：
10.1016/s1097-2765(04)00156-x
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发表时间：
2004-04-09
期刊：
影响因子：
16
通讯作者：
Cohen, GM
中科院分区：
文献类型：
--
作者：
Sun, XM;Butterworth, M;Cohen, GM
泛素/蛋白酶体系统通过降解多泛素化蛋白质来调节蛋白质周转。迄今为止，所有关于细胞凋亡和蛋白酶体关系的研究都强调蛋白酶体在细胞凋亡调节中的关键作用，因为它能够降解参与细胞凋亡的调节分子。我们现在证明细胞凋亡的诱导如何调节蛋白酶体的活性。在细胞凋亡过程中，半胱天冬酶激活导致蛋白酶体 19S 调节复合物的三个特定亚基裂解：S6' (Rpt5) 和 S5a (Rpn10)，其作用是识别蛋白酶体的多泛素化底物，以及 S1 (Rpn2)，其与 S5a 和 S2 (Rpn1) 将 19S 调节复合物的盖子和底座结合在一起。这种半胱天冬酶介导的切割抑制泛素依赖性和非依赖性细胞底物（包括促凋亡分子，如 Smac）的蛋白酶体降解，因此通过提供前馈放大环来促进凋亡程序的执行。
The ubiquitin/proteasome system regulates protein turnover by degrading polyubiquitinated proteins. To date, all studies on the relationship of apoptosis and the proteasome have emphasized the key role of the proteasome in the regulation of apoptosis, by virtue of its ability to degrade regulatory molecules involved in apoptosis. We now demonstrate how induction of apoptosis may regulate the activity of the proteasome. During apoptosis, caspase activation results in the cleavage of three specific subunits of the 19S regulatory complex of the proteasome: S6' (Rpt5) and S5a (Rpn10), whose role is to recognize polyubiquitinated substrates of the proteasome, and S1 (Rpn2), which with S5a and S2 (Rpn1) holds together the lid and base of the 19S regulatory complex. This caspase-mediated cleavage inhibits the proteasomal degradation of ubiquitin-dependent and -independent cellular substrates, including proapoptotic molecules such as Smac, so facilitating the execution of the apoptotic program by providing a feed-forward amplification loop.