HPV-16E6およびE6-AP複合体は,p53のユビキチン化におけるユビキチンタンパク質リガゼとして機能する
M Scheffner1, J M Huibregtse, R D Vierstra
1Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.
Cell
|November 5, 1993
まとめ
ヒューマン・パピローマウイルス (HPV) は,ユビキチン-プロテオリチス経路を用いて分解するために腫瘍抑制剤p53を標的にします. 研究者は,E1酵素,新しいE2酵素,およびE6-E6-AP複合体を,このプロセスの重要な要因として特定しました.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 腫瘍学 腫瘍学
背景:
- ユビキチンに依存するタンパク質分解経路は,選択的なタンパク質分解に不可欠です.
- 腫瘍性ヒトパピローマウイルス (HPV) タイプ16および18は,この経路を破壊して腫瘍抑制剤p53.3を退化させます.
- HPV E6オンコタンパク質は,E6-関連タンパク質 (E6-AP) と相互作用して,p53.3を標的とする.
研究 の 目的:
- E6-E6-AP媒介のユビキチン化およびp53.3の分解に関与する要因を特定し,浄化する.
- この過程におけるユビキチン活性化酵素 (E1),ユビキチン結合酵素 (E2),およびユビキチンタンパク質結合酵素 (E3) の役割を解明する.
主な方法:
- p53のユビキチン化に関与するタンパク質因子の浄化.
- ユビキチネーション活動を評価するための生化学的測定法.
- 新規のE2酵素の特定とE3リガゼの活性の特徴.
主要な成果:
- E6-E6-AP複合体は,p53.3のユビキチン-タンパク質リガゼ (E3) として作用する.
- p53のウビキチン化には,E1酵素と以前未確認の哺乳類E2酵素が必要です.
- E6-APは,E6.6とは独立して,ユビキチン-タンパク質・リガース活性を示す.
結論:
- E6-E6-AP複合体は,E1と新しいE2と共に,p53.3のユビキチン化と分解を媒介する.
- このメカニズムは,HPVが腫瘍生成のために細胞機構をどのように利用するかを強調しています.
- E6-APは,固有のユビキチンリガゼ活性を持つ重要な成分です.
関連する概念動画
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