XIAP‐associated factor 1 (XAF1), a novel target of p53, enhances p53‐mediated apoptosis via post‐translational modification
XIAP‐associated factor 1 (XAF1), a novel target of p53, enhances p53‐mediated apoptosis via post‐translational modification
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DOI：
10.1002/mc.20807
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发表时间：
2012-05
影响因子：
4.6
通讯作者：
B. Zou;C. Chim;R. Pang;H. Zeng;Yun Dai;Rongxin Zhang;C. Lam;V. P. Tan;I. Hung;H. Lan
中科院分区：
文献类型：
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作者：
B. Zou;C. Chim;R. Pang;H. Zeng;Yun Dai;Rongxin Zhang;C. Lam;V. P. Tan;I. Hung;H. Lan
X染色体连锁凋亡抑制蛋白（XIAP）相关因子1（XAF 1）在介导细胞凋亡中的作用已有报道，但其潜在机制尚不清楚。本研究旨在研究XAF1和p53之间的相互作用，以及这种相互作用在调节人胃癌和结肠癌细胞凋亡中的功能重要性。我们首先通过染色质免疫沉淀（CHIP）试验将XAF 1鉴定为p53的新靶基因，并证明野生型p53而不是突变型p53在mRNA和蛋白水平上下调XAF 1，这主要在XAF 1高表达的条件下起作用，并且与p53和XAF 1启动子之间的物理相互作用有关。我们还发现，XAF 1的过表达导致野生型p53在有或没有DNA损伤的细胞中通过翻译后修饰激活，这导致p53核积聚及其转录活性增加，并增强p53依赖性凋亡。这些发现表明XAF 1和野生型p53之间存在潜在的新型反馈回路。© 2011 Wiley Periodicals，Inc.
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. © 2011 Wiley Periodicals, Inc.