STAT1のアルギニンメチル化は,IFNalpha/β誘発転写を調節する
1Division of Biology and UCSD Cancer Center, University of California, San Diego, Bonner Hall 3138, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Cell
|March 21, 2001
まとめ
PRMT1によるSTAT1のアルギニンメチル化は,インターフェロン誘発の転写に不可欠です. この改変により,PIAS1の結合が妨げられ,STAT1のDNA結合とインターフェロン反応が確保され,がんではしばしば失われる.
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
- 免疫学 免疫学とは
背景:
- インターフェロンのシグナル伝達は,STAT転写因子のリン酸化に依存しています.
- STATタンパク質は,保存されたN端アルギニン残基を共有しています.
研究 の 目的:
- STAT1機能におけるアルギニンメチル化の役割を調査する.
- インターフェロン反応に対するメチル化阻害の影響を調査する.
主な方法:
- PRMT1.1によるSTAT1のアルギニンメチル化が実証された.
- メチルチオアデノシン (メチルトランスファーゼ阻害剤) を利用した.
- 評価されたSTAT1-DNA結合とPIAS1関連.
主要な成果:
- STAT1のアルギニンメチル化は,IFNalpha/β誘発転写に不可欠である.
- メチルチオアデノシンは,STAT1媒介のインターフェロン反応を抑制する.
- 抑制は,非メチル化STAT1.1におけるPIAS1関連性の増加によるSTAT1-DNA結合の障害から生じる.
結論:
- アルギニンメチル化は,STAT1機能を調節する新しい翻訳後の改変です.
- アルギニンのメチル化の変化は,悪性腫瘍におけるインターフェロンの無反応を説明する可能性がある.
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