乳酸は,アナフェーズ促進複合体を改造することによって細胞サイクルを調節する
Weihai Liu1,2,3, Yun Wang1,2,4, Luiz H M Bozi1,2
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nature
|March 15, 2023
まとめ
蓄積された乳酸は,アナフェーズ促進複合体 (APC/C) を再構成するSENP1を阻害することによって,細胞分裂を直接調節する. このメカニズムは,急速に分裂するヒト細胞の細胞サイクル進行と増殖を制御します.
科学分野:
- 生物化学
- 細胞生物学
- 癌 研究
背景:
- 乳酸は,高血糖代謝による増殖細胞に豊富に含まれています.
- 細胞増殖の調節における蓄積された乳酸の役割は不明である.
研究 の 目的:
- ヒトのタンパク質の乳酸依存調節を調査する.
- 乳酸が細胞サイクル進行に影響を与えるメカニズムを特定する.
主な方法:
- 乳酸調節タンパク質を特定するための体系的なタンパク質解析
- 乳酸とSENP1とAPCの相互作用を明らかにするための生化学的分析
主要な成果:
- 乳酸蓄積は,SUMOプロテアゼSENP1を阻害することによって,アナフェーズ促進複合体 (APC/C) を再構成する.
- 乳酸はSENP1の活性部位に亜鉛を結合し,APC4のSUMOylationを安定させ,APC/CへのUBE2C結合を促進する.
- この乳酸媒介のAPC/C調節は,細胞サイクルタンパク質の適時な分解とミトスの脱出を促進します.
結論:
- 乳酸はタンパク質の機能を直接制御し,細胞のサイクルと増殖を制御する.
- 異常な乳酸の蓄積は異常なAPC/C再構成とミトスリップにつながり,抗ミトス薬を克服する可能性がある.
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