炎症を誘発する刺激は,PIAS1のIKKalpha媒介のリン酸化を誘導し,炎症と免疫を抑制する
Bin Liu1, Yonghui Yang, Vasili Chernishof
1Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Cell
|June 2, 2007
まとめ
炎症信号はIKKalphaを活性化し,PIAS1をリン酸化し,これは遺伝子の活性化を阻害することによって炎症を抑制する重要な調節因子である. このリン酸化は,PIAS1にとって不可欠です.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- トランスクリプションに関する規則
背景:
- 炎症刺激が炎症を抑制するために核に信号を送るメカニズムは,完全に理解されていません.
- 活性化されたSTAT1のタンパク質阻害剤 (PIAS1) は,小さなユビキチン関連変形剤 (SUMO) E3リガース活性を持つ転写調節剤であり,NF-kappaBとSTAT1が遺伝子プロモーターに結合することを阻害することによって免疫反応を阻害します.
研究 の 目的:
- 炎症刺激が炎症の核抑制につながるシグナル伝達経路を解明する.
- 炎症性遺伝子活性化を調節するPIAS1のリン酸化の役割を調査する.
主な方法:
- 変異研究を用いて,Ser90.0でのPIAS1リン酸化の機能を評価した.
- TNF治療を施し,野生型および変異型PIAS1と遺伝子プロモーターの関連性を分析した.
- IKKalpha,IKKbeta,およびPIAS1.1の間のインビボ相互作用が調査されました.
主要な成果:
- PIAS1は,炎症的刺激に反応して,Ser90で素早くリン酸化される.
- セル90のリン酸化は,PIAS1の転写抑制活動に不可欠である.
- 野生型のPIAS1は,Ser90A変異体ではないが,TNF治療でNF-kappaB標的遺伝子プロモーターと結合する.
- IKKbetaではなくIKKalphaはPIAS1と相互作用し,PIAS1のSUMOリガゼ活性に依存するSer90リン酸化を媒介する.
結論:
- 炎症刺激がIKKalphaを活性化するシグナル伝達経路を特定しました.
- IKKalphaは,Ser90.0でPIAS1のスモイル化依存型リン酸化を媒介する.
- このプロセスは,PIAS1.1による炎症性遺伝子活性化の即時抑制につながります.
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