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異なるVps34複合体の微分調節は,栄養ストレスとオートファギーにおけるAMPKによるものです
Joungmok Kim1, Young Chul Kim, Chong Fang
1Department of Oral Biochemistry and Molecular Biology, Research Center for Tooth and Periodontal Tissue Regeneration, School of Dentistry, Kyung Hee University, Seoul 130-701, Korea.
Cell
|January 22, 2013
まとめ
AMP活性化タンパク質キナーゼ (AMPK) は,栄養ストレス中にVps34複合体を差異的に調節する. AMPKはVps34の非オートファギーを阻害し,同時にプロオートファギーの複合体を活性化し,細胞生存とオートファギーの誘導を制御する.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- オートファギーは,栄養不足中の生存に不可欠な細胞のストレス反応です.
- クラスIIIのフォスファディチルニノシトール-3キナーゼ,Vps34は,多種多様なタンパク質複合体の中に存在する,膀の密輸とオートファギーの誘導に中心的なものです.
- AMP活性化タンパク質キナーゼ (AMPK) は,代謝調節に関与する重要な細胞エネルギーセンサーです.
研究 の 目的:
- 異なるVps34複合体の調節におけるAMPKの役割を明らかにする.
- 栄養ストレスに対する反応として,AMPKがVps34の活性を調節する方法を理解する.
- AMPK,Vps34複合体,およびオートファジー誘導の相互作用を調査する.
主な方法:
- Vps34とBeclin1.1のリン酸化部位解析について
- Vps34複合体の形成と活動の調査.
- 血糖飢餓条件下での細胞応答アッセイ
主要な成果:
- AMPKはT163/S165でVps34をリン酸化し,非自閉性のVps34の活性とPI(3) Pの産生を阻害し,飢餓中の細胞を保護する.
- AMPKはS91/S94でBeclin1をリン酸化し,プロオートファギーVps34複合体を活性化し,オートファギーを誘発する.
- プロオオトファジー複合体の成分であるAtg14Lは,AMPKによるBeclin1のリン酸化を選択的に強化し,Vps34のリン酸化を抑制し,AMPKの調節効果を誘導する.
結論:
- AMPKは,栄養ストレス中にVps34複合体を調節する上で,重要な二重の役割を果たします.
- AMPKによるVps34とBeclin1の微分リン酸化は,生存と自己死性の間の細胞運命を決定する.
- Atg14Lは,AMPKによるVps34複合体の特定の活性化または抑制の決定的な決定因子として作用し,複雑な規制ネットワークを明らかにします.
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