p53のデアセチル化は,細胞成長とアポトーシスに対するp53の効果を調節する
1Institute of Cancer Genetics, and Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.
Nature
|December 1, 2000
まとめ
転移関連タンパク質2 (MTA2) を含むNuRD複合体は,腫瘍抑制剤p53.3を脱酸化し,調節する. この脱酸化はp53に影響を及ぼします.
科学分野:
- 分子生物学は分子生物学である.
- がん研究 がん研究
- エピジェネティクス エピジェネティクス
背景:
- p53腫瘍抑制剤の活動は,アセチル化によって調節されます.
- アセチル化p53を保持するインビボのメカニズムは完全に理解されていません.
研究 の 目的:
- 生物体内でp53脱酸化のメカニズムを解明する.
- アセチル化p53のレベルと機能を調節するタンパク質を特定する.
主な方法:
- ヒストンデセチラゼ-1 (HDAC1) を含む複合体の浄化.
- これらの複合体内のp53標的タンパク質の識別.
- インビトロとインビボの相互作用研究.
- p53依存の転写活動,細胞成長停止,アポトーシスの評価.
主要な成果:
- p53の脱アセチル化は,HDAC1を含む複合体によって媒介されます.
- PIDとも呼ばれる転移関連タンパク質2 (MTA2) は,NuRD複合体の構成要素として特定され,p53.3と相互作用しています.
- PID/MTA2発現は,アセチル化p53レベルを低下させ,p53依存の転写活性化を抑制する.
- PID/MTA2はp53媒介の細胞成長停止とアポトーシスを調節する.
結論:
- PID/MTA2を通じたNuRD複合体は,p53脱エチル化において重要な役割を果たしています.
- この脱エチル化経路は,転写活動や,成長停止やアポトーシスなどの細胞反応を含む,p53機能の調節に極めて重要です.
関連する概念動画
01:23Negative 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.
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:36DNA Damage can Stall the Cell Cycle
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...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
02:36DNA Damage Can Stall the Cell Cycle
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...