title: XIAP-associated factor 1 (XAF1), a novel target of p53, enhances p53-mediated apoptosis via post-translational modification.
abstract: 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.
authors.affiliation: Department of Gastroenterology & Hepatology, The Third Affiliated Hospital of Guangzhou Medical College, Guangzhou, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zou
authors.forename: Chor S
authors.initials: CS
authors.lastname: Chim
authors.forename: Roberta
authors.initials: R
authors.lastname: Pang
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
authors.forename: Yun
authors.initials: Y
authors.lastname: Dai
authors.forename: Rongxin
authors.initials: R
authors.lastname: Zhang
authors.forename: Colin S C
authors.initials: CS
authors.lastname: Lam
authors.forename: Victoria P Y
authors.initials: VP
authors.lastname: Tan
authors.forename: Ivan F N
authors.initials: IF
authors.lastname: Hung
authors.forename: Hui Y
authors.initials: HY
authors.lastname: Lan
authors.forename: Benjamin C Y
authors.initials: BC
authors.lastname: Wong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C417551:XAF1 protein, human