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作 者:屯亮亮[1] 李贞[2] 孙红[3,4] 李亦学[1,3,4,2]
机构地区:[1]同济大学生命科学与技术学院,上海200092 [2]上海交通大学生命科学与技术学院,上海200240 [3]中国科学院上海生命科学研究院系统生物学重点实验室生物信息中心,上海200031 [4]上海生物信息技术研究中心,上海200235
出 处:《生物物理学报》2013年第7期506-514,共9页Acta Biophysica Sinica
基 金:"973"计划项目(2010CB529200)~~
摘 要:白血病是一种常见恶性肿瘤,是我国重点防治的十大恶性肿瘤之一。冬凌草甲素是一种从草药中萃取的化合物。研究表明,冬凌草甲素能够诱导肿瘤细胞凋亡,但人们对其抗癌作用的潜在分子机制还知之甚少。作者系统分析了经冬凌草甲素处理的人白血病Kasumi-1细胞的蛋白磷酸化水平变化特征,构建了蛋白位点之间磷酸化水平变化的相关性网络。不同于基因调控网络,磷酸化水平变化相关性网络呈现带状结构。网络结构显示了蛋白磷酸化信号的级联放大传递作用,以及冬凌草甲素对蛋白磷酸化水平影响的多向性。受冬凌草甲素影响而发生磷酸化水平变化的蛋白,显著富集在与控制细胞增殖、激酶结合功能、癌症相关的重要通路中。分析结果显示了冬凌草甲素影响下的蛋白磷酸化水平变化特征及其重要作用。Leukemia is one of the most common type cancer, and it is seriously concerned about the prevention and treatment in our country. Oddonin, a natural diterpenoid isolated from Rabdosia rubescens, has been reported to have potential antitumor activities. However, the mechanism is not fully understood. Here, changes in the phosphorylation level of a particular set of proteins of Kasumi-1 cells treated with oridonin were systematically analyzed. To investigate more information of the phosphorylation signals induced by oridonin, the authors constructed a correlation network by using stringent P-value criteria to show correlation linkages between changes in the phosphorylation levels of amino acid sites. The correlation network presented a band-type structure, which was different from gene regulatory network, showing the characteristics of signal propagation through the cascade which resulted in more phosphorylated amino acid sites. Proteins with changes in phosphorylation levels significantly enriched in cellular proliferation, kinase binding functions and cancer associated pathways. The analysis showes that oridonin plays important roles in adjusting the phosphorylation levels and some key characteristics of its effects.
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