I型インターフェロン受容体のアセチル化依存信号伝導
Xiaoli Tang1, Jin-Song Gao, Ying-jie Guan
1Department of Surgery, Brown University Medical School, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA.
Cell
|October 10, 2007
まとめ
サイトカイン受容体のシグナル伝達にはアセチル化が含まれます. CREB結合タンパク質 (CBP) は,インターフェロンα受容体2 (IFNAR2) をアセチラ化し,ISGF3複合体による抗ウイルス遺伝子調節を可能にします.
科学分野:
- セルラー・シグナリング
- 分子生物学は分子生物学である.
- 免疫学 免疫学とは
背景:
- サイトカイン活性化受容体は,キナーゼを勧誘することによって信号を発信する.
- 受容体のリン酸化により,SH2ドメインベアリング因子のドッキングが可能になります.
研究 の 目的:
- 1型インターフェロン (IFNα) 信号伝達におけるCREB結合タンパク質 (CBP) の役割を調査する.
- インターフェロン調節因子9 (IRF9) の募集とISGF3複合体の形成のメカニズムを解明する.
主な方法:
- コイムノプレシピテーションアッセイは,タンパク質の相互作用を研究するためのものです.
- In vitroアセチル化アッセイは,CBPの活性を決定する.
- サイト・ディレクテッド・ミュータジェネシス (Site-directed mutagenesis) で,重要な残留物を特定する.
主要な成果:
- IFNα受容体は,IFNα刺激により,細胞質CBPを勧誘する.
- CBPは,Lys399上のIFNAR2をアセチラ化し,IRF9.9のためのドッキングサイトを作成しています.
- IRF9とSTAT2のDNA結合ドメイン内のアセチル化は,ISGF3複合体の活性化と抗ウイルス遺伝子発現に不可欠です.
結論:
- CBPによって媒介されるアセチル化は,サイトカイン受容体信号伝達における重要な規制メカニズムである.
- この経路は,抗ウイルス免疫におけるアセチル化の新たな役割を強調しています.
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