p53の降解は,p53結合とトランス活性化に必要なものとは異なるHPV E6配列によって標的とすることができる
T Crook1, J A Tidy, K H Vousden
1Ludwig Institute for Cancer Research, St. Mary's Hospital Medical School, London, England.
Cell
|November 1, 1991
まとめ
ヒトパピローマウイルス (HPV) オンコプロテインE6は,がんを引き起こすタイプから腫瘍抑制剤p53を退化させ,良性型はp53に結合するが退化させない. この違いは,E6タンパク質の特定のN端末配列にあります.
科学分野:
- 腫瘍学 腫瘍学
- ウイルス学 ウイルス学 ウイルス学
- 分子生物学は分子生物学である.
背景:
- ヒトパピローマウイルス (HPV) タイプ16と18は,アノゲニタルがんと関連しています.
- HPVオンコタンパク質E6は,細胞腫瘍抑制剤p53を標的として分解する.
- HPVタイプ6と11は,通常,良性病変と関連しています.
研究 の 目的:
- 腫瘍性および良性HPV型のE6タンパク質がp53.3と相互作用し,p53.3に影響を与える異なるメカニズムを調査する.
- p53結合と分解を司るE6タンパク質の特定の領域を特定する.
主な方法:
- E6-p53複合体の形成をテストするインビトロ結合アッセイ.
- 異なるE6変異によって媒介されるp53の分解を評価するための機能検査.
- 保存されたE6タンパク質領域 (C端末とN端末) の機能的関連性に関する分析.
主要な成果:
- 腫瘍性HPVと良性HPVの両方のE6タンパク質はp53に結合する.
- 腫瘍性HPV型 (例えば,HPV16) のE6タンパク質のみが,p53を効果的に標的として分解する.
- 保存されたE6のC末端領域は,p53結合に不可欠である.
- 腫瘍性HPV型の中で保存されている特定のN端末配列は,p53の分解を誘導するために不可欠です.
- p53結合は必要ですが,E6媒介によるp53分解には不十分です.
- E6タンパク質の転写トランス活性化活動は,p53結合または分解能力とは独立しています.
結論:
- HPV E6オンコプロテインがp53分解を誘発する能力は,腫瘍性HPVタイプに限定され,特定のN末端配列に依存します.
- E6タンパク質によるp53との差異的相互作用は,さまざまなHPVタイプの独特の腫瘍性潜在力に寄与する.
- これらの分子メカニズムを理解することは,標的を絞ったがん予防と治療の開発の鍵です.
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