DJ-1 Modulates the p38 Mitogen-Activated Protein Kinase Pathway Through Physical Interaction With Apoptosis Signal-Regulating Kinase 1

被引：39

作者：

Mo, Jung-Soon ^{[1
]}

Jung, Jane ^{[1
]}

Yoon, Ji-Hye ^{[1
]}

Hong, Ji-Ae ^{[1
]}

Kim, Mi-Yeon ^{[1
]}

Ann, Fun-Jung ^{[1
]}

Seo, Mi-Sun ^{[1
]}

Choi, Yun-Hee ^{[1
]}

Park, Hee-Sae ^{[1
]}

机构：

[1] Chonnam Natl Univ, Sch Biol Sci & Technol, Hormone Res Ctr, Kwangju 500757, South Korea

来源：

JOURNAL OF CELLULAR BIOCHEMISTRY | 2010年 / 110卷 / 01期

关键词：

DJ-1; APOPTOSIS SIGNAL-REGULATING KINASE 1 (ASK1); p38 MITOGEN-ACTIVATED PROTEIN KINASE (MAPK); PROTEIN-PROTEIN INTERACTION; CELL-DEATH; PARKINSONS-DISEASE; OXIDATIVE STRESS; ER STRESS; PHOSPHORYLATION; INHIBITION; SAPK/JNK; MUTATION; PARK7; ASK1;

D O I：

10.1002/jcb.22530

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 H2O2-induced activation of apoptosis signal-regulating kinase 1 (ASK1). According to the results, the overexpression of DJ-1 inhibited H2O2-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. J. Cell. Biochem. 110: 229-237, 2010. (C) 2010 Wiley-Liss, Inc.

引用

页码：229 / 237

页数：9