XIAP-associated factor 1 (XAF1), a novel target of p53, enhances p53-mediated apoptosis via post-translational modification
| Autor: | Roberta Pang, Bing Zou, Ivan Hung, Chor S. Chim, Hui Zeng, Hui Y. Lan, Victoria P Y Tan, Rongxin Zhang, Colin S.C. Lam, Benjamin C.Y. Wong, Yun Dai |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
DNA damage Apoptosis Biology Inhibitor of apoptosis Stomach Neoplasms Cell Line Tumor Humans Promoter Regions Genetic Molecular Biology Adaptor Proteins Signal Transducing Inhibitor of apoptosis domain Regulation of gene expression Intracellular Signaling Peptides and Proteins Signal transducing adaptor protein Molecular biology Neoplasm Proteins Cell biology XIAP Gene Expression Regulation Neoplastic Colonic Neoplasms Tumor Suppressor Protein p53 Apoptosis Regulatory Proteins Protein Processing Post-Translational Chromatin immunoprecipitation |
| Zdroj: | Molecular Carcinogenesis. 51:422-432 |
| ISSN: | 0899-1987 |
| DOI: | 10.1002/mc.20807 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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