G1サイクリン-Cdkは,RNAポリメラーゼIIの局所的リン酸化により細胞循環への侵入を促進する
Mardo Kõivomägi1, Matthew P Swaffer1, Jonathan J Turner1
1Department of Biology, Stanford University, Stanford, CA 94305, USA.
まとめ
芽生えた酵母細胞の分裂は,Whi5ではなくRNAポリメラーゼIIをリン酸化するCln3-Cdk1によって引き起こされる. これは重要なプロモーターの転写を促進し,細胞サイクルと転写調節を結びつける.
科学分野:
- 分子生物学
- 細胞生物学
- 生物化学
背景:
- 細胞分裂の開始には,転写阻害剤を非活性化するサイクリン依存キナーゼ (Cdks) が含まれる.
- 芽生えた酵母では,G1サイクリンCln3-Cdk1複合体がWhi5をリン酸化し,SBFを放出し,細胞を分裂させると考えられていた.
研究 の 目的:
- Cln3-Cdk1が芽生えた酵母で細胞分裂を起こす正確なメカニズムを調査する.
- 細胞サイクルにおける Whi5 リン酸化の役割を明らかにする.
- 細胞サイクル進行と転写調節の関係を探求する.
主な方法:
- Cln3-Cdk1の基質としてWhi5をテストするための生化学的測定法
- RNAポリメラーゼIIサブユニットRpb1のリン酸化部位分析
- キナーゼをプロモーターに合成的に誘導する遺伝子実験.
主要な成果:
- Whi5 は Cln3- Cdk1 の弱い基質であることが判明しました.
- Cln3-Cdk1はRpb1のC端ヘプタペプチドのS5位置を直接リン酸化する.
- Cln3-Cdk1はSBFが調節するプロモーターに結合し,その機能はSBFをターゲットにするとCcl1-Kin28によって模倣することができます.
結論:
- Cln3-Cdk1は,SBF調節されたプロモーターでRpb1をリン酸化して細胞分裂を開始し,それによって転写を促進します.
- このメカニズムは,細胞サイクルと転写Cdksの区別を曖昧にする.
- この発見は 細胞サイクル制御と 転写過程の間の 古代の関係を強調しています
さらに関連する動画
12:02Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
27.8K
10:49A Murine Cell Line Based Model of Chronic CDK9 Inhibition to Study Widespread Non-Genetic Transcriptional Elongation Defects TEdeff in Cancers
Published on: September 26, 2019
5.8K
関連する概念動画
Positive Regulator Molecules
5.8K
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.
5.8K
Inhibition of Cdk Activity
5.0K
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...
5.0K
S-Cdk Initiates DNA Replication
4.9K
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.9K
M-Cdk Drives Transition Into Mitosis
5.8K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.8K
The Cell Cycle Control System
3.9K
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...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
3.9K
Negative Regulator Molecules
36.6K
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.
36.6K
