エストロゲン受容体によるオバルブミン遺伝子の活性化には,フォス・ジュン複合体が関与する
M P Gaub1, M Bellard, I Scheuer
1Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Faculté de Médecine, Strasbourg, France.
Cell
|December 21, 1990
まとめ
オバルブミンのプロモーターである.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- エンドクリノロジー エンドクリノロジー
背景:
- オバルブミン遺伝子プロモーターは,エストロゲン受容体 (ER) によって細胞特異の活性化に不可欠なエストロゲン反応性要素 (ERE) を有しています.
- ホルモン信号やその他の経路が遺伝子プロモーターにどのように収束するかを理解することは,複雑な生物学的調節を解読する鍵です.
研究 の 目的:
- エストロゲンおよびその他のシグナル伝達経路による卵白素遺伝子調節の基礎となる分子機構を調査する.
- オバルブミンEREと結合するタンパク質とそのトランスクリプション活性化における役割を特定する.
主な方法:
- オバルブミンプロモーターのERE.のサイト指向型変異.
- タンパク質とDNAの相互作用を検出するための電泳運動シフトアッセイ (EMSA)
- レポーター遺伝子解析 (伝染) で,プロモーターの活性を測定する.
- 断片化されたER構造を用いたタンパク質-タンパク質およびタンパク質-DNA相互作用の分析.
主要な成果:
- オバルブミンEREは,ERとエストラディオールから独立して,オンコプロテインc-Fosとc-Junを含む核タンパク質複合体を結合します.
- エストロゲン誘導性を廃止するEREの変異は,複合体の形成を防止します.
- ERE配列 (5'-TGGGTCA-3') は,ホルボルエステル誘導に不可欠であり,c-Fosとc-Jun.の標的である.
- c-Fos,c-Jun,およびERは卵白素プロモーターを同活性化し,ERのDNA結合ドメインは,この同活性化に欠かせない.
結論:
- ホルモンの誘導と信号伝導の経路は,トランスクリプションのレベルで卵白素プロモーターに収束する.
- ERは,転写因子c-Fosとc-Junと連携して,卵巣アルブミン遺伝子発現を調節し,シグナル伝達経路の複雑な相互作用を強調しています.
- 同活性化におけるERの役割は,直接のDNA結合とは独立したメカニズムを示唆し,c-Fos/c-Jun複合体とのタンパク質-タンパク質相互作用を潜在的に含む.
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