RNAポリメラーゼIII TFIIB関連因子 Brf2によるレドックスシグナル伝達

Jerome Gouge¹, Karishma Satia¹, Nicolas Guthertz¹

¹Division of Structural Biology, The Institute of Cancer Research, London SW7 3RP, UK.

Cell

|December 7, 2015

まとめ

TFIIB関連因子2 (Brf2) は,新しい酸化還元感知型転写因子である. Brf2はRNAポリメラーゼIIIの産出を調節し,酸化ストレス経路を通じて癌の発生に関与している.

科学分野:

分子生物学
構造生物学
癌研究

背景:

TFIIB関連因子2 (Brf2) は,特定の遺伝子プロモーターへのRNAポリメラーゼIII (Pol III) のリクルートに不可欠な核転写因子である.
Brf2は脊椎動物だけに存在し,腫瘍発生と関連しているが,正確なメカニズムは不明である.

研究の目的:

Pol III プロモーターにおける Brf2 機能の分子メカニズムを解明する.
Brf2の酸化還元調節における潜在的役割とそのがんへの影響について調査する.

主な方法:

ヒトのDNAプロモーターに結合したBrf2-TBP複合体の結晶構造の決定
生体細胞での Brf2 活性を評価する in vivo 機能検査
酸化ストレス反応とがん遺伝子の活性化における Brf2 の役割の分析

主要な成果:

構造分析により,Brf2依存のPol IIIプロモーターにおける詳細な分子相互作用が明らかにされた.
Brf2内の新しいリドックスセンシングモジュールは,Pol IIIトランスクリプションを調節することができる.
Brf2は酸化ストレス経路における重要な酸化還元感知トランスクリプション因子として確立された.

結論:

Brf2は,Pol IIIの転写出力を調節するユニークなリドックス感知能力を持っています.
Brf2は細胞の酸化ストレス反応に中心的な役割を果たします.
肺がんと乳がんにおける Brf2 の遺伝的活性化のためのメカニズムモデルが提案されました.

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