オンコプロテインc-Junとグルココルチコイド受容体間の機能的対抗性
R Schüle1, P Rangarajan, S Kliewer
1Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92037.
Cell
|September 21, 1990
まとめ
グルココルチコイド受容体 (GR) とJun/AP-1転写因子は,相互に遺伝子の活性化を抑制する. この新しい抑制メカニズムには,DNA結合ではなく,タンパク質の相互作用が関与し,遺伝子調節に影響を与えます.
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
- 転写因子 トランスクリプション・ファクター
背景:
- グルココルチコイド受容体 (GR) とJun/AP-1は,細胞プロセスに関与する重要な転写因子である.
- それらの相互作用を理解することは,複雑な遺伝子規制ネットワークを解読する上で極めて重要です.
研究 の 目的:
- GRとJun/AP-1の規制関係を調査する.
- これらの要因が互いの転写活動に影響を与えるメカニズムを解明する.
主な方法:
- c-JunとGRの過剰発現に関する研究.
- グルココルチコイド応答要素 (GREs) のレポーターアッセイを用いた遺伝子活性化の分析.
- GRとc-Junドメインの変異分析.
- DNA-タンパク質複合体の形成を評価するためのゲル遅延アッセイ.
主要な成果:
- c-Junの過剰発現は,GREsにおけるGR媒介遺伝子活性化を阻害した.
- GR抑制されたAP-1駆動の転写活性化.
- GRのリガンド結合とDNA結合ドメイン,およびc-Junのルシンのジッパー領域は,抑制に不可欠でした.
- バクテリアで表現されたc-Junは,GRをGREsに結合させるのに干渉した.
結論:
- GRとJun/AP-1は,転写活性化の相互抑制を示しています.
- この相互作用は,直接のDNA結合とは無関係な新しいメカニズムによって媒介され,おそらくタンパク質-タンパク質の相互作用を含む.
- これらの発見は,異なった転写因子クラスによる遺伝子発現の調節における新たな複雑な層を明らかにしています.
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