LAP2 プロテインチャペロン GLI1 ランミナとクロマチン間の移動転写を調節する

Amar N Mirza¹, Siegen A McKellar¹, Nicole M Urman¹

¹Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Cell

|December 4, 2018

まとめ

ラミナ関連ポリペプチド2 (LAP2) アイソフォームを含む新しい核シャペロニングシステムは,基礎細胞癌におけるGLI1の動きを調節する. このシステムはヘッジホッグ経路の信号伝達に影響を与え治療対象となるのです

科学分野:

細胞生物学
分子生物学
癌研究

背景:

転写因子GLI1は,基礎細胞癌 (BCC) のヘッジホッグ経路の出力に不可欠である.
耐性BCCは非典型タンパク質キナーゼCι/λ (aPKC) とHDAC1によるGLI1脱酸化が増加している.
GLI1核輸送の理解は,標的型がん治療に不可欠です.

研究の目的:

GLI1の核内移動を制御する核のシェーパーリングシステムを特定する.
GLI1の流通と活性化におけるラミナ関連ポリペプチド2 (LAP2) アイソフォームの役割を解明する.
BCCにおける信号伝達と治療戦略への影響を探求する.

主な方法:

GLI1とLAP2イソフォーム (LAP2αとLAP2β) の相互作用を調査した.
aPKCとHDAC1がGLI1脱酸化と核輸送に及ぼす影響を調査した.
核膜と核質と関連してGLI1の局所化と活性を研究した.

主要な成果:

GLI1の核シャトルを制御する LAP2のイソフォームに依存するシステムを特定した.
LAP2βは核膜にGLI1を結合し,アセチル化依存のリザーブを作成する.
LAP2αは,LAP2βと競合し,HDAC1を基板にし,aPKCは,核プラズマ活性化のためにGLI1の放出を促進する.

結論:

LAP2イソフォームは,内核膜と核質の間のGLI1核輸送を差異的に調節する.
このLAP2を介したシステムは,BCCにおけるGLI1の信号増幅器として機能する.
GLI1の核内密輸をターゲットにすると,BCCに対する潜在的な治療の機会が生まれます.

キーワード:

GLI HDAC1 についてエジホグの信号 LAP2 について LEMドメイン aPKC について基礎細胞がん核ラミナ核骨格

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