文档介绍：· ·
1392 南方医科大学学报(J South Med Univ) 2011;31(8)
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基础研究
E1A阻断ras诱导人成纤维细胞衰老机制的研究
李亦蕾 1,余乐 2
南方医科大学 1南方医院药学部,2药学院,广东广州 510515
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。
关键词:E1A;ras;癌基因;人成纤维细胞
中图分类号:R96 文献标志码:A 文章编号:1673-4254(2011)08-1392-04
Mechanism of E1A-mediated escape from ras-induced senescence in human fibraoblasts
LI Yi-lei1, YU Le2
1Department of Pharmacy, Nanfang Hospital, 2School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515,
China
Abstract: 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 R