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Expression of Recombinant Proteins in the Methylotrophic Yeast Pichia pastoris
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イーストのヒトc-Mycオンコタンパク質による転写活性化には,Maxとの相互作用が必要です
B Amati1, S Dalton, M W Brooks
1Growth Control and Development of the Cell Nucleus Laboratory, Imperial Cancer Research Fund, London, UK.
Nature
|October 1, 1992
まとめ
Mycタンパク質は,配列特異の転写活性化剤として作用し,DNA結合と遺伝子活性化のためにMaxタンパク質との二分化を必要とします. マックスホモディマーはDNAを結合するが,転写を活性化しないため,Mycの機能に敵対する可能性がある.
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:
- c-myc タンパク質 (Myc) は, Max タンパク質 (Max) との二分化により,転写活性化と DNA 結合のためのドメインを有しています.
- 既知の機能にもかかわらず,MycとMaxは直接的な転写因子として決定的に確立されていません.
- 遺伝子調節におけるMycの役割を理解することは,細胞のプロセスや疾患を理解するために不可欠です.
研究 の 目的:
- 配列特異の転写活性化剤としてのMycタンパク質の直接的な役割を調査する.
- マイクのDNA結合とトランザクティベーション能力のためにマックスタンパク質二分化の必要性を決定する.
- マックスホモジメとマイクマックスヘテロジメの機能的結果を解明する.
主な方法:
- Saccharomyces cerevisiaeをインビボモデルシステムとして利用する.
- MycおよびMaxタンパク質のDNA結合特異性を分析する.
- 異なる二分化状態でMycとMaxによって媒介される転写活性化を評価する.
主要な成果:
- Mycがシーケンス固有の転写活性化剤であることを in vivoで実証した.
- マイクのDNA結合はマックスとの二分化に依存していることが確認されました.
- マックスホモジメは,マイクマックスヘテロジメと同じDNA部位に結合するが,トランザクティベーションの可能性が欠けていることが示された.
- Max basic helix-loop-helix-leucine zipper (bHLH-Z) ドメインが,Myc bHLH-Z ドメイン自身よりも,Myc bHLH-Z ドメインに対してより高い親和性を有していることを確認しました.
結論:
- Mycは直接の転写活性化剤として機能し,Max.との異体化に左右される.
- マックスホモダイマーは,Myc媒介の転写活性化に対する抗体として作用する.
- 均衡状態にあるMyc-Maxヘテロダイマーの好ましい形成は,転写制御のための規制メカニズムを示唆する.
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