ミトゲンとp53シグナル制御細胞サイクルエントリの競合する記憶
Hee Won Yang1, Mingyu Chung1, Takamasa Kudo1
1Department of Chemical &Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature
|September 5, 2017
まとめ
人間の細胞は 遺伝信号に基づいて 増殖するか 静止状態に入るかを決定します 母細胞から子細胞に伝達されるミトゲンとストレス信号の 競合する記憶が 細胞周期のコミットメントを決定します
科学分野:
- 細胞生物学
- 分子生物学
- 遺伝学
背景:
- 細胞の増殖は組織の安定と修復に不可欠です
- 細胞循環の調節により,子細胞が細胞循環に戻るか静止状態に入るかを決定する.
- この細胞の運命決定の 根本的なメカニズムは まだ不明です
研究 の 目的:
- 人間の細胞が 細胞サイクルに入ったり出たりを 決定する方法を調べる
- 細胞の運命を決定するシグナル伝達の歴史の役割を調査する.
- 細胞サイクルを制御する分子メカニズムを解明する.
主な方法:
- 信号分子 (p53タンパク質,サイクリンD1mRNA) のミトーシス経由での伝達を追跡する.
- 子細胞におけるサイクリンD1とp21の発現を分析した.
- p21によるサイクリンD1-CDK4のステキオメトリック阻害を調査する.
- 網膜芽細胞腫 (Rb) とE2F転写プログラムへの影響を評価する.
主要な成果:
- 母細胞はDNA損傷によるp53およびミトゲン誘発サイクリンD1 (CCND1) mRNAを子細胞に伝達する.
- 子細胞におけるサイクリンD1とp21の代謝後の発現は,遺伝信号によって決定される.
- p21によるサイクリンD1-CDK4のステイキオメトリック抑制は,Rb/E2F経路経由で細胞サイクルコミットメントを制御する.
- このメカニズムにより 子細胞は 増殖の決定のために 過去の信号を統合できます
結論:
- 細胞サイクルのエントリーまたはアウトは,変数のミトゲンとストレスの信号の競合するメモリによって制御されます.
- 自然変異,記憶,競争に基づいた新しい細胞サイクル制御原理が提案されています.
- このメカニズムは 増殖する細胞集団の健康を最適化します
関連する概念動画
02:38Mitogens and the Cell Cycle
8.2K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.2K
02:36DNA Damage can Stall the Cell Cycle
10.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.2K
02:36DNA Damage Can Stall the Cell Cycle
3.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.2K
01:23Negative Regulator Molecules
38.6K
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.
38.6K
01:28The Cell Cycle Control System
5.9K
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...
5.9K
02:11The Cell Cycle Control System
14.6K
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...
14.6K