E2F-1のDNA結合機能のサイクリンAキナーゼ調節が,S相チェックポイントの抑制の基礎となっている

W Krek¹, G Xu, D M Livingston

¹Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Cell

|December 29, 1995

まとめ

哺乳類の細胞はS相にコミットし,E2F-1転写因子が細胞サイクルを進めるようにします. サイクリンAキナーゼはE2F-1のDNA結合を抑制し,秩序あるS相進行を保証し,細胞サイクル停止を防ぐ.

科学分野:

細胞生物学細胞生物学
分子生物学は分子生物学である.
遺伝学遺伝学とは

背景:

転写因子E2F-1は,細胞サイクル進行に不可欠であり,S相への入り口に必要な遺伝子を活性化します.
S相では,E2F-1はサイクリンAキナーゼと相互作用し,通常はDNA結合活動を抑制する.

研究の目的:

サイクリンAキナーゼ媒介によるE2F-1DNA結合活性抑制とS相進行の調節の機能的関連性を調査する.
細胞サイクル制御におけるこの規制的連結を妨害する結果の決定.

主な方法:

Sフェーズ中の哺乳類細胞におけるE2F-1DNA結合活動の分析.
E2F-1機能の調節におけるサイクリンAキナーゼの役割を調査する.
S相遅延/停止,再生,アポトーシスを含む細胞サイクル進行に対するE2F-1/サイクリンAキナーゼ相互作用を妨害する効果を研究する.

主要な成果:

サイクリンAキナーゼによるE2F-1DNA結合活性抑制は,秩序あるS相進行に不可欠である.
この抑制の障害は,S相の遅延または停止につながります.
断絶された結合 (再生またはアポトーシス) の結果は,DNAに結合したE2F-1のトランザクティベーションの可能性に依存します.

結論:

サイクリンAキナーゼによるE2F-1DNA結合の調節は,重要なチェックポイントメカニズムである.
Sフェーズ中のスケジュール外E2F-1結合は,特定のSフェーズチェックポイントをトリガーすることができます.
このメカニズムは,転写,DNA複製,細胞サイクル制御を統合しています.

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