p53媒介の細胞サイクル停止,アポトーシス,老化がない場合の腫瘍抑制
Tongyuan Li1, Ning Kon, Le Jiang
1Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Cell
|June 12, 2012
まとめ
腫瘍抑制タンパク質p53は,通常,細胞サイクル停止,アポトーシス,老化によって腫瘍形成を停止します. しかし,この研究は,p53がp53と異なることを明らかにしています.
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
- 腫瘍発生は,腫瘍の発生である.
背景:
- 腫瘍抑制タンパク質p53は,がんの予防に不可欠です.
- p53のカノニカルな機能には,細胞サイクル停止,アポトーシス,老化が含まれています.
- これらの腫瘍抑制メカニズムにおけるp53アセチル化の役割は完全に理解されていません.
研究 の 目的:
- 腫瘍抑制におけるp53アセチル化の役割を調査する.
- 定規のp53機能が腫瘍抑制の速度を制限しているかどうかを判断する.
- 自発的な腫瘍発生を防ぐための代替的なp53機能を探求する.
主な方法:
- p53アセチル化部位 (p53(K117R) とp53(3KR)) で特定の変異を持つマウスを生成した.
- 変異細胞におけるp53媒介細胞サイクル停止,アポトーシス,衰老を評価した.
- ミュータントマウスにおける腫瘍形成と生存をモニターした.
- エネルギー代謝と活性酸素種 (ROS) のp53の調節を評価した.
主要な成果:
- p53 ((K117R/K117R) 細胞は細胞サイクル停止と衰老を保持したが,アポトーシスを失った.
- p53 ((3KR/3KR) 細胞は,p53の3つの正規の機能 (停止,アポトーシス,老化) をすべて失った.
- p53 ((K117R/K117R) やp53 ((3KR/3KR) のマウスは,早期発症腫瘍を発症しなかった.
- p53(3KR) は代謝調節とROS除去機能を維持した.
結論:
- p53アセチル化は,その機能を差異的に調節する.
- カノニカルなp53機能は,自発的な腫瘍抑制の速度を制限するものではありません.
- 代謝調節や抗酸化機能などの非正規のp53活動が,早期発症腫瘍の予防に不可欠である.
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