Document Detail

Oxidized DJ-1 inhibits p53 by sequestering p53 from promoters in a DNA-binding affinity-dependent manner.
MedLine Citation:
PMID:  23149933     Owner:  NLM     Status:  MEDLINE    
DJ-1 is an oncogene and the causative gene for familial Parkinson's disease. Although the oxidative status of DJ-1 at cysteine 106 (C106) is thought to affect all of the activities of DJ-1 and excess oxidation leads to the onset of various diseases, the precise molecular mechanisms underlying the effects of oxidation of DJ-1 on protein-protein interactions of DJ-1 remain unclear. In this study, we found that DJ-1 bound to the DNA-binding region of p53 in a manner dependent on the oxidation of C106. Of the p53 target genes, the expression level and promoter activity of the DUSP1 gene, but not those of the p21 gene, were increased in H(2)O(2)-treated DJ-1(-/-) cells and were decreased in wild-type DJ-1- but not C106S DJ-1-transfected H1299 cells through sequestration of p53 from the DUSP1 promoter by DJ-1. DUSP1 downregulated by oxidized DJ-1 activated extracellular signal-regulated kinase (ERK) and decreased apoptosis. The DUSP1 and p21 promoters harbor nonconsensus and consensus p53 recognition sequences, respectively, which have low affinity and high affinity for p53. However, DJ-1 inhibited p21 promoter activity exhibited by p53 mutants harboring low DNA-binding affinity but not by wild-type p53. These results indicate that DJ-1 inhibits the expression of p53 target genes and depend on p53 DNA-binding affinity and oxidation of DJ-1 C106.
Izumi Kato; Hiroshi Maita; Kazuko Takahashi-Niki; Yoshiro Saito; Noriko Noguchi; Sanae M M Iguchi-Ariga; Hiroyoshi Ariga
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-12
Journal Detail:
Title:  Molecular and cellular biology     Volume:  33     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-24     Completed Date:  2013-02-21     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  340-59     Citation Subset:  IM    
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Japan.
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MeSH Terms
Apoptosis / genetics
Blotting, Western
Cell Line, Tumor
Cysteine / genetics,  metabolism
Dual Specificity Phosphatase 1 / genetics,  metabolism
Extracellular Signal-Regulated MAP Kinases / genetics,  metabolism
HEK293 Cells
Hydrogen Peroxide
Intracellular Signaling Peptides and Proteins / genetics,  metabolism*
Oligonucleotide Array Sequence Analysis / methods
Oncogene Proteins / genetics,  metabolism*
Oxidative Stress*
Parkinson Disease / genetics,  physiopathology
Promoter Regions, Genetic*
Real-Time Polymerase Chain Reaction
Tumor Suppressor Protein p53 / genetics,  metabolism*
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Oncogene Proteins; 0/PARK7 protein, human; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 52-90-4/Cysteine; 7722-84-1/Hydrogen Peroxide; EC Signal-Regulated MAP Kinases; EC protein, human; EC Specificity Phosphatase 1

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