Sir2alphaによるp53の負のコントロールは,ストレス下での細胞生存を促進します
1Institute of Cancer Genetics and Department of Pathology, College of Physicians & Surgeons, Columbia University, 1150 St. Nicholas Avenue, New York, NY 10032, USA.
Cell
|October 24, 2001
まとめ
哺乳類のSir2alphaはp53と相互作用し,その機能を阻害し,アポトーシスを抑制する. ニコチナミド (ビタミンB3) は,この脱酸化を阻害し,細胞のストレス反応とがん治療に影響を及ぼします.
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
- バイオケミストリー バイオケミストリー
背景:
- Sir2タンパク質は,代謝を遺伝子静止と老化と結びつけるNAD依存型脱酸化酵素である.
- Sir2alphaを含む哺乳類のSir2ホモログは,様々な細胞プロセスに関与しています.
研究 の 目的:
- 哺乳類のSir2alphaと腫瘍抑制剤p53.3の相互作用を調査する.
- アポトーシスと細胞のストレス反応を含むp53媒介機能の調節におけるSir2alphaの役割を明らかにする.
主な方法:
- Sir2alphaとp53.3との間の物理的な相互作用を証明するために,共免疫プレシピテーションアッセージを行います.
- Sir2alphaがp53アセチル化および脱アセチル化に及ぼす影響を評価するインビヴォおよびインビトロ実験.
- Sir2alphaまたはその変異体の存在下でのアポトーシスとストレス反応を測定するセルラーアッセイ.
主要な成果:
- 哺乳類のSir2alphaはp53と物理的に相互作用する.
- Sir2alphaはp53媒介の転写活動とDNA結合を弱める.
- ニコチナミド (ビタミンB3) は,Sir2alpha誘発のp53脱酸化を阻害し,p53アセチル化を活体内で強化する.
- Sir2alphaは,DNA損傷と酸化ストレスによって誘発されるp53-依存アポトーシスを抑制します.
- Sir2alpha点変異体の発現は,細胞をストレス誘発のアポトーシスに敏感にする.
結論:
- 哺乳類のSir2alphaは,p53の調節経路において重要な役割を果たしています.
- Sir2alphaは,p53依存アポトーシスに対する細胞の感受性を調節する.
- Sir2alpha-p53の相互作用をターゲットにすることで,がんに対する新たな治療戦略を提供することができる.
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