HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >

Oxidized DJ-1 Inhibits p53 by Sequestering p53 from Promoters in a DNA-Binding Affinity-Dependent Manner

Files in This Item:
35118_1_merged_1351241601.pdf2.58 MBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/52746

Title: Oxidized DJ-1 Inhibits p53 by Sequestering p53 from Promoters in a DNA-Binding Affinity-Dependent Manner
Authors: Kato, Izumi Browse this author
Maita, Hiroshi Browse this author →KAKEN DB
Takahashi-Niki, Kazuko Browse this author →KAKEN DB
Saito, Yoshiro Browse this author →KAKEN DB
Noguchi, Noriko Browse this author
Iguchi-Ariga, Sanae M. M. Browse this author →KAKEN DB
Ariga, Hiroyoshi Browse this author →KAKEN DB
Issue Date: Jan-2013
Publisher: American Society for Microbiology
Journal Title: Molecular and Cellular Biology
Volume: 33
Issue: 2
Start Page: 340
End Page: 359
Publisher DOI: 10.1128/MCB.01350-12
Abstract: 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 H2O2-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.
Type: article (author version)
URI: http://hdl.handle.net/2115/52746
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 有賀 寛芳

Export metadata:

OAI-PMH ( junii2 , jpcoar )

MathJax is now OFF:


 

 - Hokkaido University