p300/CBPをp53依存の信号経路に誘導する
M L Avantaggiati1, V Ogryzko, K Gardner
1Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cell
|June 27, 1997
まとめ
腫瘍抑制タンパク質p53は,転写共活性化剤であるp300と複合体を形成する. この相互作用はp53にとって極めて重要です.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
背景:
- 腫瘍抑制タンパク質p53と転写共同活性化剤CBP/p300は,細胞成長と遺伝子転写の重要な調節因子である.
- p53は遺伝子発現のポジティブとネガティブの両方のレギュレータとして機能します.
- CBP/p300は,様々な転写因子と相互作用して遺伝子活動を調節することが知られている.
研究 の 目的:
- p53とp300の相互作用を調査する.
- 遺伝子調節と細胞プロセスに対するp53-p300複合体の形成の機能的影響を明らかにする.
- p53媒介の信号伝達経路におけるp300の役割を理解する.
主な方法:
- 同免疫プレシピテーションアッセイは,p53とp300の間のタンパク質複合体の形成を証明する.
- レポーター遺伝子解析は,特定のプロモーターの転写活性を評価するためのものです.
- p53機能を抑制するためにp300の支配的-負の形態を使用した研究.
- p53媒介細胞サイクル停止 (G1) とアポトーシスの分析.
主要な成果:
- 野生型のp53と突然変異のp53は,p300と特定のタンパク質複合体を形成する.
- ワイルド型p53は,p300に依存した方法で,AP1結合部位を含むプロモーターを阻害する.
- p300は,p53-調節されたプロモーターに対するp53の転写活性と,電離放射線に対する反応を高めます.
- 支配的陰性p300は,p53媒介の転写活性化,G1停止,アポトーシスを抑制する.
結論:
- p300はp53シグナル伝達経路の重要な構成要素である.
- p53とp300の相互作用は,遺伝子発現と増殖,細胞サイクル停止,アポトーシスなどの細胞反応の調節に不可欠です.
- これらの発見は,p53機能と細胞増殖制御の基礎となる分子機構に関する新しい洞察を提供します.
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