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衰老细胞转录因子AP1/CREB结合活性对EGF的可诱导性下降

Decrease in the EGF induced AP l/CREB Sequence specific Binding Activity during Cellular Aging

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【作者】 毛泽斌张宗玉童坦君

【Author】 Mao Ze Bin Zhang Zong Yu Tong Tan Jun (Department of Biochemistry and Molecular Biology, Beijing Medical University,Beijing 100083)

【机构】 北京医科大学生物化学与分子生物学系

【摘要】 转录因子与DNA的结合是基因转录的关键环节.通过迁移位移法分析了转录因子AP1、cAMP反应元件结合蛋白(CREB)、糖皮质激素反应元件(GRE)结合蛋白在衰老细胞中的结合活性.结果表明,AP1与CREB的结合活性在衰老细胞中对表皮生长因子(EGF)的反应性低于年轻细胞;而GRE结合蛋白的结合活性在衰老细胞中对EGF的反应性无明显变化.这提示EGF不能有效刺激衰老细胞增殖可能与其转录因子结合活性的改变有关

【Abstract】 Human diploid fibroblasts undergo a limited number of population doublings in vitro and are used widely as a model of cellular aging.Despite growing evidence that cellular aging occurs as a consequence of altered gene expression,little is known about the activity of transcription factor in aging cells.They were investigated that the sequence specific binding activity of AP l,cAMP response element binding protein(CREB)and glucocorticoid response element binging protein (GREB)by gel shift assay.Reduction in the epidermal growth factor (EGF) induced AP l,CREB sequence specific bingidng activity was observed in senescent cells while no significant difference in the activity of GREB was seen between early passage and late passage cells.These data suggest that inability of senescent cells to respond to EGF stimuli might be related to altered activity of transcription factor such as AP l and CREB.

【基金】 国家自然科学基金
  • 【分类号】Q26
  • 【被引频次】3
  • 【下载频次】91
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