フォークヘッドの転写因子は,哺乳類におけるミトーシスプログラムの実行に寄与する
B Alvarez1, C Martínez-A, B M Burgering
1Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid E-28049, Spain.
Nature
|October 19, 2001
まとめ
フォークヘッド転写因子 (FKH-TFs) は,ミトーシス遺伝子を調節することによって,細胞サイクル完了を制御する. G2におけるPI(3) K/PKB経路のダウンレギュレーションは,FKH-TFの活性化と適切な細胞分裂に不可欠である.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- 細胞循環の進行は,成長因子を含む内部および外部信号によって制御されます.
- PI(3) K/PKB経路は,G1のFKH-TFsを不活性化することによって,細胞サイクルへの入り口に決定的に重要です.
- 細胞サイクル進行の内生的な制御は,制限点の後に行われます.
研究 の 目的:
- G2におけるPI(3) K/PKB経路の衰弱の役割を調査する.
- G2.におけるFKH-TF活動の機能を決定する.
- 哺乳類の細胞サイクル終結のメカニズムを解明する.
主な方法:
- PI(3) K/PKB経路調節がFKH-TF活動に及ぼす影響を調査しました.
- FKH-TF機能を評価するために,転写的に不活性なFKH変異体を使用しました.
- 分析された細胞サイクル進行,サイトキネシス,およびミトーシス遺伝子発現 (サイクリンB,Plk).
主要な成果:
- G2におけるPI(3) K/PKB経路の衰弱は,FKH-TFの転写活性化に必要である.
- PI(3) K/PKBのダウンレギュレーションやFKH-TFの活性に障害が生じると,G2/Mが停止し,サイトキネシスが失敗し,MからG1への移行が遅れる.
- FKH-TFsは,サイクリンBおよびポロ型キナーゼ (Plk) を含む主要なミトーシス遺伝子の発現を調節する.
結論:
- FKH-TFは,哺乳類の細胞サイクル完了を制御する上で重要な役割を果たします.
- 効率的なミトシス進行は,PI(3) K/PKB経路のダウンレギュレーションと,その後のFKH転写活性に依存する.
- この研究は,PI(3) K/PKB経路とFKH-TF活動のダイナミックな調節を含む細胞サイクル終結のための新しいメカニズムを明らかにしています.
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