COP1は腫瘍抑制剤であり,ETS転写因子の劣化を引き起こします
Alberto C Vitari1, Kevin G Leong, Kim Newton
1Department of Physiological Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Nature
|May 17, 2011
まとめ
ユビキチンリガゼCOP1 (RFWD2とも呼ばれる) は,ETV1,ETV4,ETV5.5を退化させ,腫瘍抑制剤として作用する. その喪失は前立腺がんの発症と侵襲性を促進する.
科学分野:
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- プロトオンコゲンであるETV1,ETV4,ETV5は前立腺がんで頻繁に変化する.
- 発展に不可欠な彼らの翻訳後の規制は,ほとんど理解されていません.
研究 の 目的:
- ETV1,ETV4,ETV5.5の規制当局を特定する.
- 前立腺がんにおけるCOP1の役割を調査する.
主な方法:
- COP1までにETV1の劣化を評価するためのウビキチネーションアッセイ.
- COP1の結合モチーフのための前立腺がん転位 (TMPRSS2:ETV1) の分析.
- マウスモデルにおける前立腺特異的なCOP1欠乏症.
- COP1およびETV1の変異のためのヒト前立腺がんのサンプル分析.
主要な成果:
- COP1は,ETV1,ETV4,ETV5.5をあらゆる場所に存在させ,劣化させます.
- 前立腺がんの転位により,COP1無感のETV1変種が生じる.
- マウスのCOP1欠乏症は,ETV1レベルを上昇させ,多発性および新生前病変を引き起こす.
- COP1とPTENの減少は前立腺腺がんの侵入性を高めます.
- 人間の前立腺がんでは,COP1の減少と,ETV1.1の上昇が見られます.
結論:
- COP1は,ETV1,ETV4,ETV5.5を否定的に調節する腫瘍抑制剤です.
- COP1のダウンレギュレーションは,前立腺上皮細胞の増殖と腫瘍発生を促進します.
- トランスロケーションまたは遺伝子喪失によるCOP1不活性化は,前立腺がんの発症において選択的優位性をもたらします.
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