レチノブラストーマのタンパク質は,E2F部位を陽性から陰性要素に切り替えます

S J Weintraub¹, C A Prater, D C Dean

¹Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.

Nature

|July 16, 1992

まとめ

網膜芽細胞腫タンパク質 (Rb) -E2F複合体は,E2F部位に結合することによって,遺伝子転写を積極的に静止させます. この結合はRbに依存している.

科学分野:

分子生物学は分子生物学である.
細胞サイクル規制について
遺伝子転写遺伝子転写

背景:

E2Fサイトは,アデノウイルス初期の遺伝子と細胞サイクル進行のための重要なプロモーター要素です.
E2Fタンパク質は,細胞サイクルタンパク質Rbと複合体を形成し,以前はE2Fを無効化すると考えられていた.

研究の目的:

遺伝子転写におけるRb-E2F複合体の機能的役割を調査する.
細胞サイクル中のE2F活動にRbが影響するメカニズムを解明する.

主な方法:

E2FのプロモーターサイトでのRb-E2F複合体の活動分析.
活性Rb.b.の存在と欠如におけるE2F部位機能の調査
Rbのリン酸化状態とE2F結合および転写活動との相関.

主要な成果:

Rb-E2F複合体は転写的に活性であり,E2F部位に結合すると遺伝子発現を抑制する.
E2Fは,活性なRb.がない場合,ポジティブな転写要素として作用する.
Rb-E2Fの結合はRbのリン酸化に依存し,それは細胞サイクル中に変化する.

結論:

Rb-E2F複合体は,転写阻害による遺伝子静止に不可欠な役割を果たしています.
E2Fサイトは,Rbのリン酸化に基づく正または負の規制要素として動的に機能します.
このRbによるE2F部位の周期的調節は,細胞サイクル全体を通して遺伝子の活性化および抑制を制御する可能性があります.

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