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A novel function of peroxiredoxin 1 (Prx‐1) in apoptosis signal‐regulating kinase 1 (ASK1)‐mediated signaling pathway
Author(s) -
Kim So Yong,
Kim Tae Jin,
Lee Ki-Young
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.05.015
Subject(s) - ask1 , peroxiredoxin , thioredoxin , p38 mitogen activated protein kinases , signal transduction , microbiology and biotechnology , gene knockdown , apoptosis , kinase , chemistry , biology , oxidative stress , mapk/erk pathway , mitogen activated protein kinase kinase , protein kinase c , biochemistry , enzyme , peroxidase
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 H 2 O 2 . However, catalytic mutants of Prx1, C52A, C173A, and C52A/C173A, could not undergo H 2 O 2 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 H 2 O 2 . These findings suggest a negative role of Prx‐1 in ASK1‐induced apoptosis.