cAMP誘導後の転写衰弱は,CREBのPP-1媒介の脱酸化を必要とする
M Hagiwara1, A Alberts, P Brindle
1Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
Cell
|July 10, 1992
まとめ
cAMP反応性要素結合タンパク質 (CREB) は,最初のcAMP誘導後に脱酸化され,ソマトスタチン遺伝子転写を減少させます. タンパク質フォスファタゼ1 (PP-1) はCREBをデフォスフォリル化し,その活性の主な調節体として作用する.
科学分野:
- 分子生物学は分子生物学である.
- セルラー・シグナリング
- 遺伝子規制 遺伝子規制
背景:
- サイクルアデノシンモノフォスファート (cAMP) 信号伝達経路は,遺伝子転写を調節する.
- cAMP反応性要素結合タンパク質 (CREB) は,cAMPによって活性化される重要な転写因子である.
- CREBの調節を理解することは,様々な刺激に対する細胞の反応を解読する上で極めて重要です.
研究 の 目的:
- cAMP反応性元素結合タンパク質 (CREB) の転写活性衰弱のメカニズムを解明する.
- CREBの脱酸化に責任を負う特定のフォスファタゼを特定するために.
- このフォスファタゼが,cAMP依存遺伝子発現を調節する役割を調査する.
主な方法:
- タンパク質のリン酸化と脱リン酸化を追跡するための代謝ラベリング研究.
- フォスファターゼ阻害剤 (阻害剤1タンパク質,オカダイ酸) による治療.
- セル-133におけるCREBリン酸化とPC12細胞におけるソマトスタチン遺伝子転写の分析.
主要な成果:
- cAMP誘導後,CREBは一時的なリン酸化を経て,その後は脱リン酸化されます.
- セル-133でCREBの脱酸化は,ソマトスタチン遺伝子転写の減少と相関しています.
- フォスファターゼ阻害剤はCREBの脱リン酸化を防止し,転写応答を強化した.
- タンパク質フォスファタゼ1 (PP-1) は,CREBの脱リン酸化に起因する可能性の高いフォスファタゼとして特定されました.
結論:
- タンパク質フォスファタゼ1 (PP-1) は,cAMP反応性細胞におけるCREB活性を調節する上で重要な役割を果たします.
- PP-1は特に,CREBをSer-133で脱酸化し,それによってcAMPに依存する転写を阻害する.
- この発見は,CREB媒介遺伝子発現を制御する負のフィードバックメカニズムに関する重要な洞察を提供します.
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