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.
Mo
Jung-Soon
JS
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Yongbong-dong, Buk-ku, Gwangju 500-757, Republic of Korea.
Jung
Jane
J
Yoon
Ji-Hye
JH
Hong
Ji-Ae
JA
Kim
Mi-Yeon
MY
Ann
Eun-Jung
EJ
Seo
Mi-Sun
MS
Choi
Yun-Hee
YH
Park
Hee-Sae
HS
D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D048371:MAP Kinase Kinase 3 / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D015513:Oncogene Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1; D055503:Protein Multimerization; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D048371:MAP Kinase Kinase 3; C482530:MAP2K3 protein, human; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1