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Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets
Published on: July 7, 2010
信号に依存するコアクティベーターCBPは,pp90RSKの核標的である
T Nakajima1, A Fukamizu, J Takahashi
1Department of Cellular and Molecular Physiology Harvard Medical School Boston, Massachusetts 02115, USA.
Cell
|August 9, 1996
まとめ
成長因子はRas経路を活性化し,S6キナーゼ pp90RSKが共活性化剤CBPと結合する. この相互作用は,Ras反応性遺伝子の誘導を可能にしながら,cAMP反応性遺伝子を抑制します.
科学分野:
- 分子生物学は分子生物学である.
- 細胞シグナル伝達 細胞信号伝達
- 遺伝子規制 遺伝子規制
背景:
- 成長因子は,Rasのような信号伝達経路を利用して,細胞のプロセスを調節します.
- 循環性アデノシンモノフォスファート (cAMP) 経路は,様々な細胞反応に不可欠です.
- 信号伝達経路の交差は,複雑な細胞的結果につながる可能性があります.
研究 の 目的:
- Ras経路の活性化がcAMPシグナル伝達に影響を与えるメカニズムを解明する.
- このクロストークにおけるS6キナーゼ pp90RSKとコアクティベーターCBPの役割を調査する.
- この相互作用が特定の遺伝子の転写にどのように影響するかを理解する.
主な方法:
- インスリンまたは神経成長因子 (NGF) を使用してRas経路の活性化.
- pp90RSK-CBP複合体を検出するために共免疫プレシピテーションを用いたタンパク質-タンパク質相互作用の分析.
- CREB (cAMP反応性要素結合タンパク質) 活性検査による遺伝子転写の評価.
主要な成果:
- インスリンまたはNGFは,S6キナーゼ pp90RSKをコアクティベーターCBPに誘導した.
- pp90RSK-CBP複合体は高ステキオメトリーで形成され,6-8時間持続しました.
- pp90RSKがCBPに結合すると,cAMP反応性遺伝子の転写が抑制されるが,Ras反応性遺伝子の誘導には不可欠であった.
結論:
- Ras経路の活性化は,pp90RSK-CBP複合体を通じたcAMP信号伝達に干渉する.
- このクロスカップリングは,信号に依存したコアクティベーターのレベルで発生します.
- この研究は,RasとcAMP経路の間の信号統合の新しいメカニズムを示しています.
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