チェックポイント誘発シュゴシン-MAD2によるセパレーズのセカリン独立調節

Susanne Hellmuth¹, Laura Gómez-H², Alberto M Pendás²

¹Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

Nature

|April 24, 2020

まとめ

シュゴシン2 (SGO2) はセプラーゼ阻害剤として作用し,セキュリンを補完する.

科学分野:

細胞生物学
分子生物学
遺伝学

背景:

ユカリオット細胞における姉妹染色体の分離は,スパインドルアセンブリチェックポイント (SAC) とプロテアゼセパラーゼによって制御される.
シーキュリンは通常セパレーズを阻害し,APC/ C (アナフェーズ促進複合体) による分解はセパレーズを活性化します.
セキュリンがない場合のセプラーゼの調節は不明である.

研究の目的:

ヒトシュゴシン2 (SGO2) が体細胞における分離酵素活性を調節する役割を調査する.
SGO2が分離酶を阻害するメカニズムと,この阻害がどのように制御されるかを解明する.
染色体分離におけるSGO2とセキュリンの相互作用を理解する.

主な方法:

スピンドル・アセンブリ・チェックポイントの文脈でSGO2とMAD2の相互作用を調査した.
SGO2によるセプラーゼ調節を研究するために,セキュリン・ノックアウト細胞を使用した.
セパラーゼに対するSGO2- MAD2の抑制メカニズムと,この複合体の調節を分析するために,in vitroアッセイを行った.

主要な成果:

ヒトシュゴシン2 (SGO2) は,SACで活性化されたMAD2に結合し,SGO2- MAD2複合体を形成すると,分離酵素阻害剤として機能する.
SGO2-MAD2複合体はセプラーゼを効果的に隔離し,セプラーリン・ノックアウト細胞でセプラーリンを機能的に置き換えます.
セキュリンとSGO2の両方の損失は,早期のコヘシン分裂と細胞毒性を引き起こすため,それらの協力的役割を示唆する.
SGO2はセキュリンに似た擬似基板配列を介してその活性部位を遮断することによって分離酵素を阻害する.
セパラーゼは,APC/C依存のユビキティレーションとTRIP13とp31の作用によってSGO2-MAD2から放出されます.

結論:

細胞分裂におけるセパレーズ阻害剤としてのSGO2の新たな役割が特定された.
スピンドル・アセンブリ・チェックポイントによって監視されるセパレージのセキュリン独立メカニズムを発見した.
SGO2-MAD2複合体は,特にセキュリンが欠けるときに,分離酵素の活動を制御するための重要な保護を提供します.

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