p53誘発のアポプトシスのモデル
1The Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature
|September 26, 1997
まとめ
腫瘍抑制タンパク質p53は,酸化ストレスを含む新しい3段階のプロセスを通してアポトーシスを引き起こす. この発見は,p53について光を当てます.
科学分野:
- 分子生物学は分子生物学である.
- がん研究 がん研究
- 細胞死メカニズム 細胞死メカニズム
背景:
- 腫瘍抑制遺伝子p53は,ヒトのがんでは頻繁に不活性化され,その機能に関する研究を促しています.
- p53発現は細胞サイクル停止またはアポトーシスを誘発する可能性がありますが,p53-依存アポトーシスのメカニズムは完全に理解されていません.
- 大腸がんにおけるp53誘発の成長停止にはp21WAF1/CIP1が含まれているが,アポプトシス経路はほとんど特徴づけられていない.
研究 の 目的:
- アポトーシスの前のp53の転写標的を調査する.
- p53媒介によるプログラム細胞死の原因となる分子メカニズムを解明する.
主な方法:
- 遺伝子発現プロファイリングは,p53発現によって上調されるトランスクリプトを識別するために使用されました.
- p53発現細胞と対照細胞の7,202のトランスクリプトの分析.
- 発見を検証するために生化学的および薬理学的実験が行われました.
主要な成果:
- 7,202のトランスクリプトのうち,p53発現時に有意に増加したものはわずか14 (0.19%) であった.
- 多くのアップレギュレーションされた遺伝子が酸化ストレス反応に関与すると予測された.
- p53によって誘発される新しい3段階のアポプトシス経路が提案されました: レドックス遺伝子誘導,反応性酸素種生成,ミトコンドリア損傷.
結論:
- p53誘発のアポプトシスは,レドックス関連遺伝子の転写上調によって媒介されます.
- 反応性酸素種形成と,その後のミトコンドリアの酸化分解は,p53-依存細胞死における重要な出来事である.
- この研究は,酸化ストレスを含むp53駆動のアポトーシスの新しいメカニズムを明らかにしています.
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