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mdm-2瘤基因产物与p53蛋白形成复合体,并抑制p53介导的交换活化
J Momand1, G P Zambetti, D C Olson
1Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08544-1014.
Cell
|June 26, 1992
概括
鼠类双分钟2 (mdm-2) 瘤基因产物与p53蛋白结合. 这种相互作用抑制p53的瘤抑制活性,影响细胞瘤发生潜力.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 蛋白质p53是一种关键的瘤抑制剂.
- 鼠类双分钟2 (mdm-2) 基因编码了一种蛋白质,当过度表达时可以增强瘤发生潜力.
- mdm-2是一种假定的转录因子.
研究的目的:
- 描述和识别与p53.3复合的细胞蛋白.
- 调查mdm-2是否可以调节p53的交换激活.
- 为了确定mdm-2/p53相互作用的功能后果.
主要方法:
- 净化和表征90kd的蛋白 (p90) 与p53.5复合在一起.
- 确定p90是mdm-2基因的产物.
- 协同传染试验使用来自肌肉肌酸激酶基因的p53响应元素和表达野生类型p53和mdm-2的等离子体.
主要成果:
- 一种90kd的蛋白被净化,并被确定为mdm-2基因的产物.
- mdm-2产物与突变和野生类型的p53形成了一个紧密的复合体.
- 过度表达mdm-2抑制了p53-响应元素的p53-介导的交换活化.
结论:
- mdm-2 瘤基因产物与p53 蛋白直接相互作用.
- mdm-2 抑制了p53的转录活性.
- 这种相互作用表明,mdm-2通过不激活p53.3来促进瘤发生的机制.
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