TFIIHは,cdk8を含むメディエーター複合体によって陰性調節されます
S Akoulitchev1, S Chuikov, D Reinberg
1Howard Hughes Medical Institute, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Nature
|September 19, 2000
まとめ
サイクリン依存キナーゼ8 (cdk8) は,サイクリンHをリン酸化することによって転写を調節し,転写因子TFIIHに影響を与えます. この発見は,メディエーター複合体を,より高い生物における基礎的転写機構と結びつけている.
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
- バイオケミストリー バイオケミストリー
背景:
- サイクリン依存キナーゼ8 (cdk8) は,急性リンパ性白血病と転写調節に関与しています.
- 哺乳類のcdk8/cyclin Cと酵母のSrb10/Srb11は,RNAポリメラーゼIIホロ酵素の一部であり,キナーゼとして作用する.
- cdk8 / サイクリンC複合体は,転写を抑制するメディエーターのような複合体に見られます.
研究 の 目的:
- 転写におけるcdk8/cyclin Cの規制メカニズムを調査する.
- cdk8/cyclin Cが一般転写開始因子IIH (TFIIH) とどのように相互作用するかを決定する.
主な方法:
- 哺乳類のサイクリンHのcdk8.8によるリン酸化を調査した.
- このリン酸化がTFIIHの活性に与える影響を in vitroで評価した.
- サイクリンHに対するcdk8リン酸化を模倣したインビボ効果を調べた.
主要な成果:
- Cdk8は,哺乳類のサイクリンHを,その独特の螺旋ドメインの近くでリン酸化する.
- このリン酸化は,TFIIHの転写活性化とCTDキナーゼの活性化を阻害する.
- in vivoでサイクリンHのcdk8リン酸化を模倣することで,細胞の成長に優位負の効果をもたらした.
結論:
- Cdk8/cyclin Cは,TFIIHサブユニットをターゲットにすることで,転写を調節する.
- cdk8とTFIIHを含む規制経路は,メディエーター複合体と基礎転写機構を結びつける.
- この調節経路は,より高い生物に特異的なようです.
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