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Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets
Published on: July 7, 2010
信号依赖的协同激活器CBP是pp90RSK的核目标
T Nakajima1, A Fukamizu, J Takahashi
1Department of Cellular and Molecular Physiology Harvard Medical School Boston, Massachusetts 02115, USA.
Cell
|August 9, 1996
概括
增长因子激活Ras通路,导致S6激酶pp90RSK与协同激活剂CBP结合. 这种相互作用抑制cAMP响应基因,同时使Ras响应基因诱导.
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
- 基因法规 基因法规
背景情况:
- 增长因子利用像Ras这样的信号通路来调节细胞过程.
- 循环腺单酸盐 (cAMP) 途径对于各种细胞反应至关重要.
- 信号通路之间的交叉交谈可以导致复杂的细胞结果.
研究的目的:
- 阐明Ras路径激活影响cAMP信号的机制.
- 调查S6激酶pp90RSK和协活性剂CBP在这种交叉谈话中的作用.
- 了解这种相互作用如何影响特定基因的转录.
主要方法:
- 使用胰岛素或神经生长因子 (NGF) 激活Ras通路.
- 使用共免疫沉来检测pp90RSK-CBP复合物的蛋白质-蛋白质相互作用的分析.
- 通过CREB (cAMP-响应元素结合蛋白) 活性测试对基因转录的评估.
主要成果:
- 胰岛素或NGF诱导了S6激酶pp90RSK的招募到协活性器CBP.
- 这种pp90RSK-CBP复合体是在高静脉测量时形成的,持续了6-8小时.
- pp90RSK与CBP结合抑制了对cAMP响应基因的转录,但对Ras响应基因诱导至关重要.
结论:
- 拉斯通路的激活会干扰通过pp90RSK-CBP复合体传递cAMP信号.
- 这种交叉合发生在依赖信号的协同激活器层面.
- 这项研究表明了Ras和cAMP通路之间的信号整合的新机制.
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