遺伝子プロテオミクスクリーンによって明らかになった,サイクリンD1の発達における転写的役割
Frédéric Bienvenu1, Siwanon Jirawatnotai, Joshua E Elias
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature
|January 22, 2010
まとめ
細胞サイクルタンパク質であるサイクリンD1は,マウスの発達中の転写にも機能する. それは,Notch1遺伝子プロモーターにCBPを勧誘し,その発現を調節し,網膜の祖先細胞の増殖に影響を与えます.
科学分野:
- 分子生物学は分子生物学である.
- 発達生物学 発達生物学とは
- がん研究 がん研究
背景:
- サイクリンD1は,ヒトの癌で頻繁に過剰発現される重要な細胞循環調節剤です.
- サイクリンD1の完全な機能は,正常な発達と腫瘍形成において,ほとんど不明のままである.
研究 の 目的:
- 細胞サイクルにおける役割を超えて,サイクリンD1のインビボ機能を調査する.
- 遺伝子-プロテオミックアプローチを用いて,新しいサイクリンD1結合タンパク質と転写標的を特定する.
主な方法:
- フラグとヘマグルチニンでタグ付けされたサイクリンD1ノックインマウスモデルの開発.
- サイクリンD1相互作用タンパク質を特定するための高通量質量スペクトロメトリ.
- ゲノム全体の位置分析のためのDNAマイクロアレイ (ChIP-chip) と結合したクロマチンの免疫プレシピテーション.
主要な成果:
- サイクリンD1は,マウスの発達中に活性的に転写された遺伝子のプロモーターを結合することが判明しました.
- 発達中の網膜において,サイクリンD1はCREB結合タンパク質 (CBP) をNotch1遺伝子プロモーターに勧誘する.
- サイクリンD1の喪失は,CBPの徴募を減らし,Notch1の発現を減らし,網膜の祖先細胞の増殖を阻害しました.
結論:
- サイクリンD1はマウスの発達における重要なインビヴォの転写機能を有しており,これはカノニカルな細胞サイクルにおける役割とは独立している.
- 特定された"遺伝子・プロテオミック"アプローチは,様々なタンパク質の in vivo 機能を研究するための汎用的なツールです.
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