DJ-1 modulates the p38 mitogen-activated protein kinase pathway through physical interaction with apoptosis signal-regulating kinase 1.

DJ-1 has been reported as a gene linked to early onset familial Parkinson's disease, and is functionally involved in transcriptional regulation and oxidative stress-induced cell death. To understand the role of DJ-1 in cellular stress, this study investigated DJ-1's effect on stress-activated protein kinase signaling and H(2)O(2)-induced activation of apoptosis ...
signal-regulating kinase 1 (ASK1). According to the results, the overexpression of DJ-1 inhibited H(2)O(2)-induced activation of ASK1 as well as the activation of downstream kinases in the p38 mitogen-activated protein kinase (MAPK) signaling cascade. The results of both in vivo binding and kinase studies have revealed that ASK1 is the direct target of DJ-1, whereas it has shown no effect on either MKK3 or p38. DJ-1 blocked both the homo-oligomerization of ASK1 and inhibited ASK1 activity. Taken together, our data strongly suggest that DJ-1, by directly inhibiting ASK1, may act as a negative regulator in ASK1 signaling cascades.
Mesh Terms:
Cell Line, Enzyme Activation, Humans, Intracellular Signaling Peptides and Proteins, MAP Kinase Kinase 3, MAP Kinase Kinase Kinase 5, MAP Kinase Signaling System, Models, Biological, Oncogene Proteins, Oxidative Stress, Protein Binding, Protein Multimerization, p38 Mitogen-Activated Protein Kinases
J. Cell. Biochem.
Date: May. 01, 2010
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