转录因子QM的磷酸化过程与炎癌转化关系的研究

项目名称： 转录因子QM的磷酸化过程与炎癌转化关系的研究

项目编号： No.91229116

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 陈依军

作者单位： 中国药科大学

项目金额： 90万元

中文摘要： 非可控性炎症的恶性转化过程与转录因子的调控密切相关，现有证据表明转录因子参与了这一转化过程中的多个环节。本课题组通过蛋白组垂钓技术在肿瘤细胞中发现具有显著抗炎和抗肿瘤活性的小白菊内酯与转录因子QM的磷酸化形式具有高度亲和力。基于NF-κB是小白菊内酯发挥抗炎作用的直接靶标，NF-κB可提高蛋白激酶JNK活性，并且QM可被JNK磷酸化，我们推测在非可控性炎症恶性转化过程中存在NF-κB—JNK—QM磷酸化—炎症因子—肿瘤细胞发生间的新途径，从而导致癌症。本课题将以QM的磷酸化过程为切入点，阐述NF-κB激活JNK磷酸化QM，磷酸化后的QM介导IL-1、IL-6、COX2、VEGF等相关基因和炎症细胞因子异常表达调控的分子机制。本课题研究有望确定非可控性炎症恶性转化过程中多条网络调控通路共享的新型关键分子，增加对复杂网络调控系统的认知，为最终揭示非可控性炎症恶性转化的分子机制作出贡献。

中文关键词： 人核糖体蛋白L10；转录组测序；肿瘤发生；信号网络；磷酸化

英文摘要： The malignant transformation of unresolved inflammation is closely related to the expression and regulation of transcription factors, and transcription factors are usually involved in multiple steps of the malignant transformation. Parthenolide is a sesquiterpene lactone extracted from medical plants, which exhibits both anti-inflammatory and antitumor activities, depending on a wide range of intracellular signaling networks. Previous finding in our laboratory indicated that the phosphorylated QM is a target of parthenolide in tumor cells by proteomics analysis. Given that parthenolide can effectively inhibit NF-κ B in tumor cells, NF-κ B can promote the activity of JNK, and JNK is able to phosphorylate QM, we hypothesize that the pathway of NF-κ B -JNK-QM phosphorylation -inflammatory cytokine release-tumorigenesis may represent a new avenue in the malignant transformation from unresolved inflammation. Taken the phosphorylation of QM as a major step, the present project will conduct following studies to investigate the above hypothesis: a) NF-κ B activates JNK to phosphorylate QM; b) phosphorylated QM regulates the expression of cytokines, such as IL-1, IL-6, COX2, VEGF; and c) QM mediated cytokine releases result in the malignant transformation of unresolved inflammation in mice. This project will provide a ke

英文关键词： Human ribosomal protein L10；Transcriptome；Tumorigenesis；Signaling Network；Phosphorylation