在p53-依赖信号通路中招募p300/CBP
M L Avantaggiati1, V Ogryzko, K Gardner
1Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cell
|June 27, 1997
概括
瘤抑制剂p53蛋白与p300形成复合体,这是一个转录协活性剂. 这种相互作用对p53至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 瘤抑制蛋白p53和转录协活性器CBP/p300是细胞生长和基因转录的关键调节者.
- p53作为基因表达的积极和消极调节器.
- 已知CBP/p300与各种转录因子相互作用,调节基因活性.
研究的目的:
- 为了研究p53和p300之间的相互作用.
- 阐明p53-p300复合体形成对基因调节和细胞过程的功能后果.
- 了解p300在p53介导信号通路中的作用.
主要方法:
- 同免疫沉试验证明了p53和p300之间的蛋白质复合体形成.
- 记者基因测试用于评估特定促进体上的转录活性.
- 使用p300的主导阴性形式抑制p53功能的研究.
- 对p53介导的细胞周期停止 (G1) 和细胞亡的分析.
主要成果:
- 野生类型和突变p53与p300形成一个特定的蛋白质复合体.
- 野生类型的p53,以p300依赖的方式,抑制含有AP1结合位点的促进剂.
- p300增强了p53对p53-调节的促进体的转录活性,以及对电离辐射的反应.
- 一个主导负的p300抑制p53-介导的转录激活,G1停止,和亡.
结论:
- p300是p53信号通路的重要组成部分.
- p53和p300之间的相互作用对于调节基因表达和细胞反应,如增殖,细胞循环停止和细胞亡至关重要.
- 这些发现提供了对p53功能和细胞增殖控制背后的分子机制的新见解.
相关概念视频
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...