E1A阻断ras诱导人成纤维细胞衰老机制的研究  

Mechanism of E1A-mediated escape from ras-induced senescence in human fibraoblasts

作　　者：李亦蕾[1] 余乐[2] 

机构地区：[1]南方医科大学南方医院药学部,广东广州510515 [2]南方医科大学药学院,广东广州510515

出　　处：《南方医科大学学报》2011年第8期1392-1395,共4页Journal of Southern Medical University

基　　金：广东省自然科学基金(S2011010003868);南方医科大学南方医院院长基金(2008B027)

摘　　要：目的通过研究E1A氨基端细胞生长调节蛋白结合活性对其阻断ras诱导的细胞衰老的影响,以明确在人类成纤维细胞E1A阻断ras诱导的细胞衰老的机制。方法采用原代培养的人类成纤维细胞,通过灭活或干扰与E1A氨基端相关的细胞生长调节蛋白,包括Rb家族蛋白、p300/CBP、p400,利用细胞生长曲线确定这些蛋白结合活性对于E1A阻断ras诱导的细胞衰老的作用。结果单纯灭活Rb家族蛋白不能阻断ras诱导的细胞衰老,而同时灭活Rb和p300/CBP即可阻断ras诱导的细胞衰老。结论 Rb和p300/CBP的结合活性均是E1A阻断ras诱导的人成纤维细胞细胞衰老所必需的。Objective To study the effect of binding activities of the NH2 terminus of E1A to the proteins regulating cell growth on ras-induced cell senescence and explore the mechanism of E1A-mediated escape from ras-induced senescence by E1A in human fibroblast.Methods In primary human fibroblasts,the proteins regulating cell growth in association with E1A NH2 terminus,including the Rb family proteins,p300/CBP,and p400,were inactivated or interfered.The effect of alterations in the binding activities of these proteins on cell senescence bypass mediated by E1A was evaluated by cell growth curve.Results Inactivation of Rb family proteins alone was not sufficient to rescuer as-induced cell senescence,whereas inactivation of both the Rb proteins and p300/CBP blocked ras-induced senescence of human fibroblasts.Conclusion Rb and p300/CBP binding activities are both required for E1A to bypass ras-induced senescence in human fibroblasts.

关 键 词：E1A RAS 癌基因 人成纤维细胞 

分 类 号：R346[医药卫生—基础医学]