細胞サイクル制御における新しい規制モチーフは,サイクリンD/CDK4の特定の阻害を引き起こす
M Serrano1, G J Hannon, D Beach
1Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Nature
|December 16, 1993
まとめ
最近発見されたタンパク質p16は,サイクリン依存キナーゼ4 (CDK4) に結合し,その活性を抑制する. この発見は,細胞分裂と増殖を制御する新しい規制フィードバック回路を明らかにしています.
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:
- ユカリオット細胞分裂は,サイクリン依存キナーゼ (CDK) によって調節されます.
- CDK4とD型サイクリンは,G1期間の細胞増殖を制御する.
- CDK4は,増殖細胞核抗原であるサイクリン,およびp21.と複合体を形成する.
研究 の 目的:
- 人間のp16タンパク質を分離し,特徴づけること.
- p16とCDK4.4の相互作用を調査する.
- CDK4/サイクリンD酵素活性に対するp16の影響を測定する.
主な方法:
- 人間のp16補完DNAの分離.
- タンパク質結合と酵素阻害を研究するための生化学分析.
主要な成果:
- 人間のp16cDNAが成功裏に分離されました.
- p16がCDK4と結合することが示されました.
- p16はCDK4/サイクリンD酵素の触媒活性を抑制する.
結論:
- p16はCDK4/サイクリンDの活性抑制剤として作用する.
- p16は,CDK4,D型サイクリン,および網膜芽細胞腫タンパク質との調整フィードバック回路に関与しています.
- この相互作用は,機能的なレチノブラストーマタンパク質が欠けている細胞において特に重要である.
関連する概念動画
Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
The Cell Cycle Control System
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...


