Cyclophilin A regulates JNK/p38-MAPK signaling through its physical interaction with ASK1

被引：48

作者：

Kim, Hunsung ^{[1
,2
]}

Oh, Yoojung ^{[1
,2
]}

Kim, Kiyoon ^{[1
,2
]}

Jeong, Suyun ^{[1
,2
]}

Chon, Suk ^{[3
]}

Kim, Daehong ^{[4
]}

Jung, Min Hyung ^{[5
]}

Pak, Youngmi Kim ^{[6
]}

Ha, Joohun ^{[1
,2
]}

Kang, Insug ^{[1
,2
]}

Choe, Wonchae ^{[1
,2
]}

机构：

[1] Kyung Hee Univ, Sch Med, Dept Biochem & Mol Biol, Project BK21,Med Res Ctr Bioreact React Oxygen Sp, Seoul 130701, South Korea

[2] Kyung Hee Univ, Sch Med, Inst Biomed Sci, Seoul 130701, South Korea

[3] Kyung Hee Univ, Sch Med, Dept Endocrinol & Metab, Seoul 130701, South Korea

[4] Natl Canc Ctr, Mol Imaging & Therapy Branch, Gyeonggydo 410769, South Korea

[5] Kyung Hee Univ, Coll Med, Dept Physiol, Seoul 130731, South Korea

[6] Kyung Hee Univ, Sch Med, Dept Obstet & Gynecol, Seoul 130701, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 464卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Apoptosis; Apoptosis signal-regulating kinase 1(ASK1); Cyclophilin A (CypA); Mitogen-activated protein kinase (MAPK); Oxidative-stress; OXIDATIVE STRESS; APOPTOSIS; PROTECTS; PATHWAYS; DISEASE; COMPLEX; DEATH; CELL;

D O I：

10.1016/j.bbrc.2015.06.078

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Cyclophilin A (CypA), a member of the immunophilin family, is predominantly localized in the cytoplasm. The peptidylprolyl isomerase (PPIase) activity of CypA has been demonstrated to be involved in diverse cellular processes, including intracellular protein trafficking, mitochondrial function, pre-mRNA processing, and maintenance of multiprotein complex stability. In this study, we have demonstrated that CypA regulates apoptosis signaling-regulating kinase 1 (ASK1) through its direct binding. ASK1 is a member of MAPK kinase kinase (MAP3K) family, and selectively activates both JNK and p38 MAPK pathways. Here, we also report that CypA negatively regulates phosphorylation of ASK1 at Ser966, and that CypA reduces ASK1 and its downstream kinases of the JNK and p38 signaling. ASK1 is known to induce caspase-3 activation and apoptosis, and CypA inhibited ASK1-mediated apoptosis by decrease in caspase-3 activity under cellular stress conditions. Overall, we conclude that CypA negatively regulates ASK1 functions by its physical interaction with ASK1. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：112 / 117

页数：6

共 20 条

[1]

Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities [J].