基础研究E1A阻断ras诱导人成纤维细胞衰老机制研究.pdfVIP

·1392 · 南方医科大学学报（J South Med Univ ） 2011;31(8) ·基础研究· E 1A 阻断ras 诱导人成纤维细胞衰老机制的研究 1 2 李亦蕾 ，余 乐 1 2 南方医科大学 南方医院药学部，药学院，广东 广州 510515 摘要：目的通过研究E 1A 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E 1A 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E 1A 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E 1A 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E 1A 阻断ras 诱导的人成纤维细胞细胞衰老所必需的。 关键词：E 1A ；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 1 2 LI Yi-lei , YU Le 1Department of Pharmacy, Nanfang Hospital, 2 School 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 Rb family proteins alone was not sufficient to rescue