ストレス誘発のリン酸化と,p38 MAP キナーゼによる転写因子CHOP (GADD153) の活性化
1Department of Medicine, Skirball Institute of Biomolecular Medicine, New York University Medical Center, 10016, NY, USA.
Science (New York, N.Y.)
|May 31, 1996
まとめ
細胞のストレスは,CHOP (C/EBP同質タンパク質) を介して成長と分化に影響します. P38 MAPキナーゼによるCHOPのストレス誘発のリン酸化は,その転写活動と細胞の分化における役割を高めます.
科学分野:
- 分子生物学は分子生物学である.
- 細胞のストレス反応は,
- シグナルトランスデュークション
背景:
- CCAAT/強化剤結合タンパク質同類タンパク質 (CHOP) は,細胞のストレス反応に関与する転写因子である.
- CHOPの蓄積とリン酸化は,ストレス条件下で観察される.
- CHOPの調節における特定のキナーゼの役割は,依然として調査の分野です.
研究 の 目的:
- ストレス誘発によるCHOPのリン酸化におけるp38ミトゲン活性化タンパク質キナーゼ (MAPK) の役割を調査する.
- CHOPリン酸化が転写活動と脂肪細胞の分化に及ぼす機能的影響を決定する.
主な方法:
- 精製されたタンパク質を用いたインビトロキナーゼアッセイ.
- 特定のp38 MAPK阻害剤 (SB203580) を利用したインビボ試験.
- CHOPの転写活動と脂肪分化マーカーの分析.
主要な成果:
- p38 MAPKは,セルリン残基78および81にCHOPを直接リン酸化する.
- p38 MAPKの阻害により,ストレス誘発性CHOPリン酸化が vivoで廃止されました.
- リン酸化により,CHOPの転写活性化機能が強化された.
- リン酸化は,脂肪細胞の分化に対するCHOPの抑制効果に不可欠でした.
結論:
- p38 MAPKによるCHOPリン酸化は,細胞のストレスと遺伝子発現の変化を結びつける重要なメカニズムです.
- このリン酸化イベントは,転写活性化と分化抑制の両方でCHOPの機能を調節する.
- CHOPは,p38のシグナル伝達と,ストレス下での細胞の運命決定の間の重要な仲介者として機能します.
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