結合されたCDKとネットワークオシレータによる細胞サイクル転写のグローバル制御
David A Orlando1, Charles Y Lin, Allister Bernard
1Department of Biology, Duke University, Durham, North Carolina 27708, USA.
Nature
|May 9, 2008
まとめ
芽生えた酵母菌の遺伝子発現は,細胞分裂のタイミングが決められている. サイクリン依存キナーゼ (CDK) はこれに影響しますが,転写因子ネットワークは周期的な遺伝子転写を独立に駆動します.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- 細胞生物学 細胞生物学
背景:
- 遺伝子発現のタイミングは,Saccharomyces cerevisiaeの細胞サイクル進行に極めて重要です.
- 転写因子ネットワークとサイクリン依存キナーゼ (CDK) は,細胞周期依存転写の調節に関与しています.
- 以前の研究では,CDKの活性が主に周期的な遺伝子転写を制御することを示唆していました.
研究 の 目的:
- 全球細胞サイクル転写プログラム制御におけるサイクリン-CDK複合体の役割を調査する.
- 細胞サイクル中の周期的な転写プログラムを確立する責任はCDKにだけあるかどうかを判断する.
主な方法:
- ゲノム全体の転写ダイナミクスは,S相およびミトスサイクリンが欠けている芽生えた酵母変異体で分析されました.
- これらのサイクリン欠乏変異体における細胞サイクル進行をモニタリングした.
主要な成果:
- 周期的に発現する遺伝子の有意な部分は,サイクリン変異体において異常発現を示した.
- G1/S境界での細胞サイクル停止にもかかわらず,周期性遺伝子の約70%が予定された周期性発現を維持しました.
- サイクリン-CDKの活動は,グローバルな周期的転写プログラムの唯一の決定因子ではありません.
結論:
- サイクリン依存キナーゼは,細胞サイクル転写の調節に役割を果たしますが,プログラム全体を独占的に制御することはありません.
- 定期的な遺伝子転写は,転写因子ネットワークの新興特性であるようです.
- この転写因子ネットワークは,細胞サイクル振動器として機能し,CDK振動器と独立してまたは協調して動作します.
さらに関連する動画
関連する概念動画
02:39Positive 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.
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
01:28The 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...
02:11The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
02:11The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
02:34Inhibition 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...