転写因子CREBのダイナミック・グリコシル化:遺伝子調節における潜在的な役割
Nathan Lamarre-Vincent1, Linda C Hsieh-Wilson
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Journal of the American Chemical Society
|May 29, 2003
まとめ
記憶に不可欠な循環型AMP反応性要素結合タンパク質 (CREB) は,脳内でO-GlcNAcの糖化を受けます. この変更は,CREBを妨げています.
科学分野:
- 神経科学は神経科学である.
- 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:
- CREB (cyclic AMP-responsive element-binding protein) は,長期記憶の形成に不可欠な転写因子である.
- O-GlcNAcのグリコシレーションは,様々な細胞プロセスに関与するダイナミックな翻訳後の改変である.
研究 の 目的:
- CREBが哺乳類の脳でO-GlcNAcをグリコシル化しているかどうかを調査する.
- CREB O-GlcNAcのグリコシライゼーションが,その転写活動に及ぼす機能的影響を決定する.
主な方法:
- CREB.上のO-GlcNAc変異を検出するためのウェスタン・ブロッティング.
- CREBのTAFII130との相互作用とその転写活性を評価するためのインビトロアッセイ.
主要な成果:
- CREBは,そのQ2領域内の2つの特定の部位でO-GlcNAcをグリコシル化していることが示されています.
- このグリコシライゼーションイベントは,CREBとTAFII130タンパク質の相互作用を妨げます.
- CREBのO-GlcNAcグリコシル化により,その転写活性がin vitro抑制される.
結論:
- O-GlcNAcのグリコシレーションは,脳内の遺伝子発現を制御する役割を果たします.
- この発見は,O-GlcNAcの改変と,記憶と情報保存の基礎となる分子機構との関係を確立しています.
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