Jun dimerization protein 2 is a critical component of the Nrf2/MafK complex regulating the response to ROS homeostasis

被引：0
作者：
S Tanigawa
C H Lee
C S Lin
C C Ku
H Hasegawa
S Qin
A Kawahara
Y Korenori
K Miyamori
M Noguchi
L H Lee
Y C Lin
C L Steve Lin
Y Nakamura
C Jin
N Yamaguchi
R Eckner
D-X Hou
K K Yokoyama
机构：
[1] Faculty of Agriculture,Department of Dermatology
[2] Kagoshima University,Department of Environmental Medicine
[3] Kaohsiung Chang Gung Memorial Hospital and Chang Gung University,Department of Biochemistry and Molecular Biology
[4] College of Medicine,undefined
[5] Graduate Institute of Medicine,undefined
[6] Kaohsiung Medical University,undefined
[7] Graduate School of Pharmaceutical Sciences,undefined
[8] Chiba University,undefined
[9] Hunan Agriculture University,undefined
[10] RIKEN BioResource Center,undefined
[11] School of Dentistry,undefined
[12] Kaohsiung Medical University,undefined
[13] Cancer Center,undefined
[14] Kaohsiung Medical University Hospital,undefined
[15] NYU School of Medicine,undefined
[16] Rutgers New Jersey Medical School,undefined
[17] Rutgers,undefined
[18] The State University of New Jersey,undefined
[19] 11Present address: Department Kidney Development,undefined
[20] Institute of Molecular Embryology and Genetics,undefined
[21] Kumamoto University,undefined
[22] Kumamoto,undefined
[23] Japan,undefined
来源：
Cell Death & Disease | 2013年 / 4卷
关键词：
JDP2; Nrf2–MafK; ROS regulation; antioxidant enzymes; antioxidation;
D O I：
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中图分类号：
学科分类号：
摘要：
Oxidative stress and reactive oxygen species (ROS) are associated with diseases such as cancer, cardiovascular complications, inflammation and neurodegeneration. Cellular defense systems must work constantly to control ROS levels and to prevent their accumulation. We report here that the Jun dimerization protein 2 (JDP2) has a critical role as a cofactor for transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and small Maf protein family K (MafK) in the regulation of the antioxidant-responsive element (ARE) and production of ROS. Chromatin immunoprecipitation–quantitative PCR (qPCR), electrophoresis mobility shift and ARE-driven reporter assays were carried out to examine the role of JDP2 in ROS production. JDP2 bound directly to the ARE core sequence, associated with Nrf2 and MafK (Nrf2–MafK) via basic leucine zipper domains, and increased DNA-binding activity of the Nrf2–MafK complex to the ARE and the transcription of ARE-dependent genes. In mouse embryonic fibroblasts from Jdp2-knockout (Jdp2 KO) mice, the coordinate transcriptional activation of several ARE-containing genes and the ability of Nrf2 to activate expression of target genes were impaired. Moreover, intracellular accumulation of ROS and increased thickness of the epidermis were detected in Jdp2 KO mice in response to oxidative stress-inducing reagents. These data suggest that JDP2 is required to protect against intracellular oxidation, ROS activation and DNA oxidation. qPCR demonstrated that several Nrf2 target genes such as heme oxygenase-1, glutamate–cysteine ligase catalytic and modifier subunits, the notch receptor ligand jagged 1 and NAD(P)H dehydrogenase quinone 1 are also dependent on JDP2 for full expression. Taken together, these results suggest that JDP2 is an integral component of the Nrf2–MafK complex and that it modulates antioxidant and detoxification programs by acting via the ARE.
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页码：e921 / e921
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