DJ-1 restores p53 transcription activity inhibited by Topors/p53BP3.
DJ-1 is a multi-functional protein that plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in onset of Parkinson's disease. Here, we report that DJ-1 bound to Topors/p53BP3, a ring finger protein binding to both topoisomerase I and p53, in vitro and in vivo and that both proteins were colocalized in cells. DJ-1 and p53 were then found to be sumoylated by Topors in cells. It was also found that DJ-1 bound to p53 in vitro and in vivo and that colocalization with and its binding to p53 were stimulated by UV irradiation of cells. Transcription activity of p53 was found to be abrogated by Topors concomitant with sumoylation of p53 in a dose-dependent manner, and DJ-1 restored its repressed activity by releasing the sumoylated form of p53. These findings suggest that DJ-1 positively regulates p53 through Topors-mediated sumoylation.
Shinbo
Yumi
Y
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Taira
Takahiro
T
Niki
Takeshi
T
Iguchi-Ariga
Sanae M M
SM
Ariga
Hiroyoshi
H
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009363:Neoplasm Proteins / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000494:pharmacology*; D015513:Oncogene Proteins / Q000235:genetics* / Q000494:pharmacology*; D000071617:Protein Deglycase DJ-1; D015398:Signal Transduction; D014157:Transcription Factors / Q000494:pharmacology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D014466:Ultraviolet Rays; D016335:Zinc Fingers
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C120157:TOPORS protein, human; D044767:Ubiquitin-Protein Ligases; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D004264:DNA Topoisomerases, Type I