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Papers In Press, published online ahead of print January 30, 2006
Dept. of Cell Biology, The University of Alabama at Birmingham, Birmingham, AL 35294-0005
Corresponding Author: xchen{at}uab.edu
The p53 family consists of p53, p63, and p73, each of which has multiple isoforms due to transcription at two separate promoters and alternative splicing. While p53 is a bona fide tumor suppressor, p63 appears to have a Janus-faced function as a tumor suppressor and an oncogene. In order to address the two opposing functions of p63, we analyzed its target genes. Here, we found that GPX2, which encodes a glutathione peroxidase, is up-regulated by p63 but not p53. Accordingly, a unique responsive element was found in the promoter of the GPX2 gene, which can be activated and bound by p63 but not p53. We also found that upon over-expression, GPX2 alleviates the apoptotic response of MCF7 cells to oxidative stresses. Interestingly, the protective function of GPX2 is p53-dependent. Likewise, we showed that a deficiency in GPX2 renders MCF7 cells susceptible to oxidative stress-induced apoptosis. Given that the delta N isoform of p63 is frequently over-expressed in tumor cells, the observations here provide an insight into the mechanism by which some isoforms of p63 serve as a pro-survival factor by up-regulating GPX2 to reduce the p53-dependent oxidative stress-induced apoptotic response.
J. Biol. Chem, 10.1074/jbc.M512655200
Submitted on November 28, 2005
Revised on January 25, 2006
Accepted on January 30, 2006
GPX2, a direct target of p63, inhibits oxidative stress-induced apoptosis in a p53-dependent manner
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