A novel function of peroxiredoxin 1 (Prx-1) in apoptosis signal-regulating kinase 1 (ASK1)-mediated signaling pathway.
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.
Kim
So Yong
SY
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.
Kim
Tae Jin
TJ
Lee
Ki-Young
KY
D000595:Amino Acid Sequence; D017209:Apoptosis; D002384:Catalysis; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry / Q000235:genetics; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047468:Immunoprecipitation; D048848:MAP Kinase Kinase Kinase 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics; D008969:Molecular Sequence Data; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
D035683:MicroRNAs; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D048848:MAP Kinase Kinase Kinase 5; D003545:Cysteine