ジュンプロトオンコゲンは,その産物であるジュン/AP-1によって正に自己調節される
1Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, 92093.
Cell
|December 2, 1988
まとめ
転写因子Jun/AP-1は,自身の遺伝子発現を直接刺激する. このポジティブなフィードバックループは,TPAのような腫瘍プロモーターに反応する細胞の信号を放大します.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- がん研究 がん研究
背景:
- 転写因子Jun/AP-1はTRE配列に結合し,TPAや血清因子などの刺激に反応して細胞遺伝子の転写を強化する.
- Jun/AP-1の活動は,翻訳後の改変と遺伝子発現の増加により,TPA刺激細胞で上昇しています.
研究 の 目的:
- TPAに対する反応として,Jun/AP-1活動の規制メカニズムを調査する.
- 自身の遺伝子の転写活性化におけるJun/AP-1の役割を明らかにする.
主な方法:
- 結合プロモーター領域のAP-1結合部位のサイト特異性変異.
- Jun/AP-1によるTPA誘導とトランス活性化の分析.
主要な成果:
- Junプロモーターの高い親和性サイトに結合するJun/AP-1は,TPA誘発の転写を媒介する.
- この結合部位の変異はTPA誘導とJun/AP-1トランス活性化を廃止した.
- Jun転写が,その遺伝子産物である Jun/AP-1 によって直接刺激されることを実証した.
結論:
- Jun/AP-1自己調節は,正のフィードバックループを形成し,Jun遺伝子転写を直接刺激する.
- この正の調節ループは,タンパク質キナーゼCの活性化によって開始された細胞信号を長引かせる可能性が高い.
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