通过氨酸甲基化调节p53活性
Sergei Chuikov1, Julia K Kurash, Jonathan R Wilson
1Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Nature
|November 5, 2004
概括
瘤抑制剂p53蛋白质的作用
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 细胞生物学 细胞生物学
背景情况:
- p53是一种关键的瘤抑制蛋白.
- 它的活动是通过翻译后的修改来调节的,包括稳定.
- 了解p53调节是癌症研究的关键.
研究的目的:
- 确定调节p53.3的新机制.
- 为了研究氨酸甲基化在p53活性中的作用.
- 通过Set9.9阐明p53甲基化的结构基础.
主要方法:
- 使用Set9甲基转移酶进行氨酸甲基化试验.
- 对p53局部化和稳定性对甲基化反应的分析.
- 使用X射线晶体学对Set9-p53复合物的结构研究.
主要成果:
- Set9甲基转移酶在单个残留物中专门甲基化p53.
- 甲基化p53表现出增强的核定位和稳定性.
- Set9介导的甲基化会影响p53目标基因的表达.
- 晶体结构揭示了Set9.9对p53的分子识别.
结论:
- 通过Set9进行氨酸甲基化是p53.3的新型调节机制.
- 这种修改会影响p53的稳定性,局部化和基因调节.
- 结构洞察力为理解p53-Set9相互作用提供了基础.
相关概念视频
Negative 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.
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Covalently 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.
Abnormal 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...
Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
DNA 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...


