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コレステロールと脂質ホメオスタシスのSREBP制御に必要なARC/メディエーターサブユニット
Fajun Yang1, Bryan W Vought, John S Satterlee
1Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, Massachusetts 02129, USA.
Nature
|June 27, 2006
まとめ
ステロール調節要素結合タンパク質 (SREBPs) は,脂質ホメオスタシスに不可欠なARC105サブユニット経由で遺伝子を活性化します. この研究は,ARC105を明らかにしています.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- バイオケミストリー バイオケミストリー
背景:
- ステロール調節要素結合タンパク質 (SREBPs) は,コレステロールと脂肪酸の代謝を調節する重要な転写因子です.
- 以前の研究では,SREBPがCREB結合タンパク質 (CBP) /p300 KIXドメインと相互作用して,未知のメカニズムで共同活性化剤複合体を募集することが示されました.
研究 の 目的:
- SREBPがコアクティベーター複合体を勧誘するメカニズムを解明する.
- SREBP媒介による遺伝子活性化に関与するアクティベーター・リクルート・コファクター (ARC) /メディエーター複合体の特定のサブユニットを特定する.
- 脂質ホメオスタシスにおけるARC105の役割を調査する.
主な方法:
- 核磁共振 (NMR) スペクトロスコーピーは,ARC105.5におけるSREBP結合ドメインの構造を決定する.
- アクティベータ結合ドメインの比較分析.
- 遺伝子機能を研究するために,Caenorhabditis elegansにおけるRNA干渉 (RNAi).
主要な成果:
- SREBPはARC105 (MED15) サブユニットを利用して標的遺伝子を活性化します.
- 構造分析により,ARC105はCBP/p300 KIXドメインに似た3ヘリックスバンドルを有しているが,CREBとc-Myb.に対する固有結合特異性があることが明らかになった.
- C. elegansでは,ARC105のホモログであるMDT-15は脂肪酸ホメオスタシスに不可欠であり,SBP-1と共に油酸合成を調節する.
- オレイン酸サプリメントは,sbp-1およびmdt-15 RNAi ネマトダの表型欠陥を回復させた.
結論:
- ARC105は,SREBPに依存する遺伝子調節の重要な効果因子です.
- ARC105サブユニットは,メタゾーンにおける脂質ホメオスタシスの制御に保存された役割を果たします.
- 転写因子とコアクティベーターサブユニットの間の特定の相互作用は,遺伝子調節の複雑さを強調しています.
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