期刊
MOLECULAR CARCINOGENESIS
卷 51, 期 5, 页码 422-432出版社
WILEY
DOI: 10.1002/mc.20807
关键词
XAF1; p53; apoptosis; gastric cancer; colon cancer
资金
- University of Hong Kong [HKU-200807176136]
- Science and Technology Programme of Guangzhou, China [2008J1-C261-3]
The role of X chromosome-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) in mediating apoptosis has been reported but the underlying mechanism remains unclear. The present study was designed to examine the putative interaction between XAF1 and p53 and the functional importance of this interaction in regulation of apoptosis in human gastric and colon cancer cells. We first identified XAF1 as a novel target gene of p53 by the chromatin immunoprecipitation (CHIP) assay and demonstrated that wild-type p53, but not mutant p53, down-regulated XAF1 at both mRNA and protein levels, which acted mostly under the condition of high expression of XAF1 and was associated with the physical interaction between p53 and the XAF1 promoter. We also found that the over-expression of XAF1 led to activation of wild-type p53 via post-translational modification in cells with or without DNA damage, which resulting in p53 nuclear accumulation and its increased transcriptional activity and enhancing p53-dependent apoptosis. These findings suggest that a potential novel feedback loop exists between XAF1 and wild-type p53. (c) 2011 Wiley Periodicals, Inc.
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