HIF1AはCDK8-メディエーターを用いて,低酸素への反応としてRNAPII延長を刺激する
Matthew D Galbraith1, Mary A Allen, Claire L Bensard
1Howard Hughes Medical Institute, University of Colorado at Boulder, Boulder, CO 80309, USA.
Cell
|June 11, 2013
まとめ
低酸素誘導因子1-α (HIF1A) は,CDK8-Mediator複合体を用いて,低酸素に対する細胞応答の重要なステップであるRNAポリメラーゼII (RNAPII) の延長を促進します.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
背景:
- 低酸素誘導因子1-α (HIF1A) は,低酸素状態への細胞適応に不可欠である.
- HIF1Aが遺伝子発現,特にRNAポリメラーゼII (RNAPII) の活性を調節する正確なメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- 低酸素期におけるRNAPII活性調節におけるHIF1Aの役割を明らかにする.
- HIF1A媒介遺伝子誘導に関与するメディエーター複合体の特定の成分を特定する.
主な方法:
- クロマチン免疫降水 (ChIP) 測定は,タンパク質の結合を評価するための測定である.
- 遺伝子発現の変化を定量化するために,活性RNAPIIのグローバル分析.
- タンパク質の相互作用を研究するための生化学分析.
主要な成果:
- HIF1AはCDK8-Mediator複合体を勧誘し,その染色体結合またはヒストンアセチル化とは無関係にRNAPII延長を刺激する.
- CDK8は,CDK19ではないが,HIF1A標的遺伝子の誘導に不可欠である.
- HIF1Aは,CDK8-Mediator経由で超伸縮複合体 (SEC) の結合を促進し,それによってRNAPIIの停止を緩和する.
結論:
- HIF1AはCDK8-Mediator複合体を利用して,低酸素期におけるRNAPII延長と遺伝子発現を制御する.
- CDK8は,HIF1Aシグナル伝達と転写活性化を結びつける重要なメディエーターとして作用します.
- これらの発見は,低酸素反応とがん生物学におけるHIF1AとCDK8を伴う新しいメカニズムを明らかにしています.
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