Abstract
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.
Highlights
DJ-1, a ubiquitously expressed protein identified as an oncogene product, was first found to be involved in breast cancer, lung cancer, and prostate cancer [1,2,3,4]
The cleaved form of caspase-9 (p35) was detected from cells transfected with EGFP using antibodies specific to cleaved caspase-9, whereas it was not detected from cells expressing DJ-1-EGFP (Fig. 1A)
In the present study we show that overexpression of DJ-1 down-regulates Bax in N2a, 293, and A549 cells, which harbor p53, but not in H1299 cells, the p53-null cells
Summary
DJ-1, a ubiquitously expressed protein identified as an oncogene product, was first found to be involved in breast cancer, lung cancer, and prostate cancer [1,2,3,4]. Our study implicates that the inhibition of p53 transcriptional activity by DJ-1 may play a role in control of p53-Bax-caspase apoptotic pathway. DJ-1 Protects against Hydrogen Peroxide-induced Apoptosis by Down-regulating Bax in a p53-dependent Manner—To investigate whether DJ-1 protects against cell death in our cellular model, Neuro2a (N2a) cells, a mouse neuroblastoma cell line, were transiently transfected with DJ-1-EGFP or EGFP alone.
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