A novel function of peroxiredoxin 1 (Prx-1) in apoptosis signal-regulating kinase 1 (ASK1)-mediated signaling pathway |
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Authors: | Kim So Yong Kim Tae Jin Lee Ki-Young |
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Institution: | Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Cheoncheon-Dong 300, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, Republic of Korea. |
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Abstract: | We report a novel function of peroxiredoxin-1 (Prx-1) 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 redox-sensitive 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 ASK1-induced apoptosis. |
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Keywords: | ASK1 apoptosis signal-regulating kinase 1 Prx-1 peroxiredoxin 1 Trx thioredoxin H2O2 hydrogen peroxide shRNA short hairpin RNA JNK c-Jun NH2-terminal kinase TNF-α tumor necrosis factor alpha |
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