CREMとCREBのCBP独立の活性化は,LIMのみのタンパク質ACTによって行われます
G M Fimia1, D De Cesare, P Sassone-Corsi
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-ULP, Illkirch, Strasbourg, France.
Nature
|March 23, 1999
まとめ
研究者らは,新種のタンパク質であるACTを発見し,それは丸におけるCREM (cAMP応答要素調節器) 転写を活性化する. このアクティベーターは,従来のリン酸化とCBPの相互作用を回避し,男性生殖細胞における遺伝子調節のための新しい経路を示唆しています.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- 生殖生物学 生殖生物学
背景:
- CREB (cAMP応答要素結合タンパク質) とCREM (cAMP応答要素調節器) による転写活性化には,通常,リン酸化と共同活性化剤CBPの相互作用が必要です.
- CREMは,メオト後期における雄性生殖細胞の遺伝子発現に不可欠である.
研究 の 目的:
- 精巣におけるCREM媒介の転写活性化に関与する新しいタンパク質を特定する.
- 新しく特定された丸特有の活性化剤の機能とメカニズムを特徴づける.
主な方法:
- テストシスのcDNAライブラリからCREMと相互作用するタンパク質を分離するために2つのハイブリッドスクリーンを使用しました.
- 酵母と哺乳類の細胞での機能的測定は,CREMの転写活動に対する特定されたタンパク質の影響を評価するために使用されました.
- 新型タンパク質の発現パターンは,組織と発達に特異的な方法で分析されました.
主要な成果:
- 精巣から派生したcDNAが,LIMのみのタンパク質をコードし,ACT (精巣内のCREMの活性化剤) と呼ばれる.
- ACTは特にCREMと関連しており,組織および発達的に調節された方法でCREMと協調して発現します.
- ACTは,CREMの転写活動を強く刺激し,Ser117のリン酸化とCBPの相互作用の必要性を回避します.
結論:
- ACTは,カノニカルメカニズムとは独立したCREMとCREBによる転写活性化のための新しい経路を表しています.
- ACTは,異なる細胞の分化プログラム,特に男性の生殖細胞の発達に関与する,組織特異的共活性化剤の新種を構成する可能性がある.
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