Yap1はα-カテニンの下流で作用し,表皮の増殖を抑制する
Karin Schlegelmilch1, Morvarid Mohseni, Oktay Kirak
1Stem Cell Program, Children's Hospital, Boston, MA 02115, USA.
Cell
|March 8, 2011
まとめ
ヒッポス経路の重要な成分であるYap1は,表皮幹細胞の増殖と哺乳類の皮膚の組織増殖を制御する. アルファ-カテニンは負の調節剤として作用し,Yap1の活性を調節し",群衆制御"メカニズムに貢献します.
科学分野:
- 細胞生物学 細胞生物学
- 発達生物学 発達生物学とは
- 皮膚科 皮膚科について
背景:
- 組織特異的な幹細胞の増殖は,発達と再生の間に臓器のサイズ決定のために厳格に規制されています.
- この制御を制御する分子機構,特に皮膚では,完全に理解されていません.
- ヒッポシグナル伝達経路とそのエフェクタ Yap1 は,様々な文脈で細胞増殖と臓器の大きさのレギュレータとして知られています.
研究 の 目的:
- 皮膚生物学におけるHippo経路の転写効果因子であるYap1の役割を調査する.
- Yap1が表皮幹細胞の増殖と組織拡張を調節する分子メカニズムを解明する.
- 皮膚ホメオスタシスの文脈でYap1のアップストリームレギュレータを特定する.
主な方法:
- 機能の獲得と喪失の研究は,上皮幹細胞におけるYap1の役割を評価するために使用されました.
- Yap1のTEAD転写因子との相互作用を調査しました.
- Yap1の活性に対するα-カテニンの調節作用を分析し,そのリン酸化と14-3-3およびPP2Aフォスファタゼとの相互作用を含む.
主要な成果:
- Yap1は,表皮幹細胞の増殖と皮膚組織の膨張の重要な調節剤として特定されました.
- Yap1は,TEADの転写因子との相互作用によってその機能を果たします.
- α-カテニンはYap1の上流負の調節体であることが判明し,14-3-3とPP2Aフォスファタゼとの相互作用を調節することにより,その活性とリン酸化状態を制御します.
結論:
- Yap1は,哺乳類の皮膚における表皮幹細胞の増殖能力の重要な決定因子である.
- Yap1は",群衆制御"に似た組織サイズを制御する分子回路における重要な効果因子として作用する.
- α-カテニンは,Yap1の活性を調節する上で重要な役割を果たし,皮膚の細胞密度と腫瘍抑制の感知に貢献します.
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