ヒト原発がん遺伝子c-junは,転写因子AP-1の構造的および機能的特性を有するDNA結合タンパク質をコードする
1Howard Hughes Medical Institute, Department of Biochemistry, University of California, Berkeley, CA 94720.
Science (New York, N.Y.)
|December 4, 1987
まとめ
人間のプロトオンコゲンc-junは,転写因子AP-1に似たDNA配列を結合するタンパク質をコードする. この発見は,c-junを遺伝子調節と癌の発症と関連付けています.
科学分野:
- 分子生物学は分子生物学である.
- 腫瘍学 腫瘍学
- 遺伝子規制 遺伝子規制
背景:
- 核腫瘍遺伝子の産物は,遺伝子調節を変化させ,潜在的に癌を引き起こす可能性があります.
- 核オンコタンパク質の作用の正確なメカニズムは完全に理解されていません.
- 腫瘍遺伝子のv-junは,酵母転写因子GCN4のDNA結合ドメインとホモロジーを共有し,AP-1と似たDNA配列を認識する.
研究 の 目的:
- ヒト原発がん遺伝子c-junと増強剤結合タンパク質AP-1との関係を調査する.
- c-jun製品が遺伝子発現を調節するためにDNA配列と直接相互作用するかどうかを判断する.
主な方法:
- 人間の原発がん遺伝子の分離とクローン化 c-jun.
- タンパク質を生成するためにクローン化されたc-junの細菌発現.
- 人間AP-1とのクロス反応性試験のためのv-junペプチドに対する抗体の生成.
- 浄化されたAP-1の部分アミノ酸配列解析.
主要な成果:
- c-junの推論されたアミノ酸配列は,v-junと80%以上の同一性を示した.
- c-junの細菌発現は,AP-1と同一のDNA結合特性を持つタンパク質を生成した.
- v-junペプチドに対する抗体は,ヒトのAP-1と特異的に反応した.
- AP-1の部分シーケンシングは,c-junタンパク質と共有するトリプティックペプチドを明らかにした.
結論:
- 構造と機能の類似性は,AP-1がc-jun.によってコードされていることを強く示唆しています.
- c-junプロトオンコゲン製品は,特定のDNA配列を直接結合して遺伝子発現を調節する.
- この発見は,細胞の成長と腫瘍形成に影響を与えるc-junによって制御される遺伝子の識別を可能にします.
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