保存されたユビキチネーション経路は,食事制限への反応として長寿を決定する
Andrea C Carrano1, Zheng Liu, Andrew Dillin
1Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nature
|June 26, 2009
まとめ
食事制限は,C. elegans.のHECT E3ユビキチンリガゼWWP-1およびUBC-18酵素を通して寿命を延ばす. WWP-1は,WWP-1という
科学分野:
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
- 老化に関する研究
背景:
- ダイエット制限 (DR) は,様々な種で寿命を延ばす保存介入です.
- これは,栄養素感知と生存経路を含む保存されたメカニズムを暗示しています.
- これらの経路を理解することは,健康的な老化を促進する戦略を開発するために不可欠です.
研究 の 目的:
- 食事制限への反応として寿命を調節するHECT E3ユビキチンリガゼWWP-1の役割を調査する.
- WWP-1による長寿のための下流の要因と酵素的要件を特定する.
- DRによる寿命延長に対するWWP-1の具体的な貢献を明らかにする.
主な方法:
- モデル生物であるCaenorhabditis elegansを使用した.
- wwp-1 (野生型および触媒死変異体) とubc-18.cの発現を操作した.
- 任意の食事と食事制限の条件下での推定寿命.
- 研究された遺伝的依存性には,ファ4およびダフ16が含まれています.
主要な成果:
- wwp-1の過剰発現は,C. elegans.で寿命を最大20%延長した.
- WWP-1の長寿促進効果はFOXA転写因子pha-4に依存していたが,DAF-16はそうではなかった.
- wwp-1機能の喪失はDR誘発の長寿を抑制し,その触媒作用は不可欠であった.
- E2ユビキチン結合酵素UBC-18は,WWP-1と相互作用し,DR誘発の長寿に不可欠かつ特異的であることが判明しました.
結論:
- WWP-1は,C. elegans.の食事制限への反応として,寿命のポジティブレギュレータとして作用します.
- UBC-18と結合したWWP-1のユビキチン・リガース活性が,DR媒介の長寿に決定的である.
- これらの発見は,栄養素の限られた条件下で寿命を調節するWWP-1とUBC-18を含む新しいユビキチンリガゼ経路を明らかにしています.
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