通过Fos结合序列,TGF-β1抑制了跨素/斯特罗梅利辛基因表达
L D Kerr1, D B Miller, L M Matrisian
1Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232.
Cell
|April 20, 1990
概括
转化生长因子β1 (TGF-β1) 通过将含有Fos的复合物与特定的促进物元素结合,抑制了跨素基因表达. 这种机制对TGF-β1至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 基因规则 基因规则
背景情况:
- 转化生长因子β1 (TGF-β1) 是细胞过程的关键调节者,包括矩阵金属蛋白酶的表达.
- 众所周知,矩阵降解酶的转/斯特罗梅利辛受生长因子和瘤基因的调节.
- TGF-β1对基因表达产生抑制作用的精确分子机制尚未完全阐明.
研究的目的:
- 为了确定参与TGF-β1介导的转素基因表达抑制的特定DNA元素和蛋白质因子.
- 阐明c-fos原瘤基因产物 (Fos) 在TGF-β1信号通路中的作用.
- 为了研究不同TGF-β1抑制基因中调节元件的保存.
主要方法:
- 促成体分析,以确定跨素基因促成体中的TGF-β1抑制元件 (TIE).
- 电泳运动转移试验 (EMSAs) 检测核蛋白与TIE结合.
- 西方斑分析和基因表达研究,以评估Fos诱导的作用.
主要成果:
- 被称为TIE的转素促进体中的10bp元素被确定为TGF-β1诱导的生长因子抑制的关键.
- 发现这种TIE序列在其他TGF-β1受抑制基因中保持.
- 在TGF-β1刺激细胞中,与TIE结合的核蛋白复合体含有Fos蛋白,而Fos诱导是抑制作用所必需的.
结论:
- 转素基因表达的TGF-β1抑制是由含有Fos的蛋白质复合体与TIE促进体序列的结合介导的.
- 这些发现揭示了TGF-β1涉及c-fos原型瘤基因的新型基因调节机制.
- 这种调节途径可能是TGF-β1介导的基因抑制的保存机制.
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