MAPキナーゼによる転写因子p62TCFのリン酸化は,c-fosプロモーターにおける三元複合体の形成を刺激する
H Gille1, A D Sharrocks, P E Shaw
1Max-Planck-Institut für Immunbiologie, Spemann Laboratories, Freiburg, Germany.
Nature
|July 30, 1992
まとめ
ミトゲン活性化タンパク質 (MAP) キナーゼは,転写因子p62TCFをリン酸化し,c-FOS遺伝子プロモーターへの結合を強化する. このリン酸化は,成長因子誘発のc-FOS遺伝子発現に極めて重要です.
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
- 腫瘍遺伝子 (オンコゲネス) とは
背景:
- プロトオンコゲンc-FOSの転写は成長因子によって急速に誘発される.
- p67SRFとp62TCFの三元複合体は,c-FOS誘導に不可欠な血清応答要素と結合する.
- ミトゲン活性化タンパク質 (MAP) キナーゼはミトゲンによって活性化され,増殖信号を伝達する.
研究 の 目的:
- c-FOS転写の調節におけるMAPキナーゼの役割を調査する.
- MAPキナーゼがc-FOS血清応答要素の三元複合体の形成に直接影響するかどうかを判断する.
主な方法:
- MAPキナーゼとp62TCFを用いたインビトロリン酸化アッセイ.
- スイスの3T3細胞を,表皮成長因子 (EGF) とインスリンで刺激する.
- c-FOS遺伝子発現と三元複合体の形成の分析.
主要な成果:
- MAPキナーゼリン酸化物p62TCF in vitroは,三重複合体の形成を促進する.
- EGF治療はMAPキナーゼを活性化し,c-FOS発現と活性三元複合体の形成につながります.
- MAPキナーゼを活性化しないインスリン治療は,c-FOS転写を誘導したり,三元複合体の形成を高めるのに失敗します.
結論:
- MAPキナーゼ媒介によるp62TCFのリン酸化は,成長因子誘発c-FOS原発がん遺伝子発現における重要なステップである.
- この研究は,MAPキナーゼシグナル伝達経路とc-FOS転写の調節を関連付けています.
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