A novel function of peroxiredoxin 1 (Prx-1) in apoptosis signal-regulating kinase 1 (ASK1)-mediated signaling pathway
A novel function of peroxiredoxin 1 (Prx-1) in apoptosis signal-regulating kinase 1 (ASK1)-mediated signaling pathway
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DOI：
10.1016/j.febslet.2008.05.015
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发表时间：
2008-06-11
期刊：
影响因子：
3.5
通讯作者：
Lee, Ki-Young
中科院分区：
文献类型：
--
作者：
Kim, So Yong;Kim, Tae Jin;Lee, Ki-Young
我们报道了过氧化物还毒素-1 （Prx1）在ask1介导的信号通路中的新功能。Prx-1通过ASK1的硫氧还蛋白结合域与ASK1相互作用，这种相互作用被H2O2高度诱导。然而，Prx1、C52A、C173A和C52A/C173A的催化突变体不能进行H2O2诱导的相互作用，这表明Prx-1的氧化敏感催化活性是与ASK1相互作用所必需的。Prx-1过表达抑制ASK1的激活，并导致下游信号级联如MKK3/6和p38通路的抑制。在Prx-1敲低的细胞中，ASK1、p38和JNK在H2O2的作用下被快速激活，导致细胞凋亡。这些发现提示Prx-1在aski诱导的细胞凋亡中起负作用。(c) 2008年欧洲生化学会联合会。Elsevier B.V.版权所有。
We report a novel function of peroxiredoxin-1 (Prx1) in the ASK1-mediated signaling pathway. Prx-1 interacts with ASK1 via the thioredoxin-binding domain of ASK1 and this interaction is highly inducible by H2O2. However, catalytic mutants of Prx1, C52A, C173A, and C52A/C173A, could not undergo H2O2 inducible interactions, indicating that the redoxsensitive catalytic activity of Prx-1 is required for the interaction with ASK1. Prx-1 overexpression inhibited the activation of ASK1, and resulted in the inhibition of downstream signaling cascades such as the MKK3/6 and p38 pathway. In Prx-1 knockdown cells, ASK1, p38, and JNK were quickly activated, leading to apoptosis in response to H2O2. These findings suggest a negative role of Prx-1 in ASKI-induced apoptosis. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.