DJ-1 decreases Bax expression through repressing p53 transcriptional activity.
DJ-1, originally identified as an oncogene product, is a protein with various functions in cellular transformation, oxidative stress response, and transcriptional regulation. Although previous studies suggest that DJ-1 is cytoprotective, the mechanism by which DJ-1 exerts its survival functions remains largely unknown. Here we show that DJ-1 exerts its cytoprotection through inhibiting p53-Bax-caspase pathway. DJ-1 interacts with p53 in vitro and in vivo. Overexpression of DJ-1 decreases the expression of Bax and inhibits caspase activation, whereas knockdown of DJ-1 increases Bax protein levels and accelerates caspase-3 activation and cell death induced by UV exposure. Our data provide evidence that the protective effects of DJ-1 on apoptosis are associated with its ability of decreasing Bax level through inhibiting p53 transcriptional activity.
Laboratory of Molecular Neuropathology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
Jun
J
Fan
Haigang
H
Ren
Nali
N
Jia
Erkang
E
Fei
Tian
T
Zhou
Peng
P
Jiang
Mian
M
Wu
Guanghui
G
Wang
D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D015513:Oncogene Proteins / Q000502:physiology*; D000071617:Protein Deglycase DJ-1; D014158:Transcription, Genetic / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000502:physiology; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D020169:Caspases