Functional characterization of the p53 binding site in the human PYNOD promoter

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• 作者：Qi Zeng^a ; Daxiang Lu^a ; Qingliang Tang^a ; Li Tian^a ; Huadong Wang^a ; Suisheng Tang^b ; Chaofeng Hu^a ; ^{thcf@jnu.edu.cn}
• 关键词：Innate immunity ; Promoter ; PYNOD ; p53 Binding site ; NOD-like receptors
• 刊名：Human Immunology
• 出版年：2012
• 期刊代码：75_01988859
• 类别：bio
• 出版时间：April, 2012
• 卷：73
• 期：4
• 页码：355-363
• 文件大小：2319 K

摘要

Many members of the NOD-like receptor (NLR) family play important roles in pathogen recognition and inflammation. However, human PYNOD, an NLR-like protein consisting of a pyrin domain and a nucleotidebinding and oligomerization domain (NOD), has been reported to inhibit inflammatory signals. Using bioinformatics, we found a completely preserved canonical p53 binding site in the PYNOD core promoter (鈭?28 to 鈭?37 bp) both in humans and in chimpanzees. In this study, we investigated the characterization and biologic function of this binding site in vitro. The results show that either deletion of the p53 binding elements within the PYNOD promoter or treatment with p53 inhibitor (PFT-伪) could significantly reduce PYNOD promoter activity and PYNOD expression as detected by the enhanced green fluorescent protein (EGFP) reporter system, reverse transcription-polymerase chain reaction, and Western blot respectively. Furthermore, the chromatin immunoprecipitation (ChIP) method confirmed that p53 could bind to the PYNOD promoter. Our findings suggest that the p53 binding site plays a positive role in regulating PYNOD gene expression, which may maintain an efficient balance between defense and self-inflicted injury in respond to pathogen invasion.