描述p53 p.T253I作为一种病原性突变的特征,该突变是Li-Fraumeni综合征的基础
Nathaniel C Holcomb1, Amanda M Harrington1,2, Hong Pu1
1The Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, United States of America.
PloS one
|December 5, 2025
概括
在儿科上腺皮癌中发现了一种新的TP53突变 (p.T253I). 这种TP53变体损害了瘤抑制,可能将其与Li-Fraumeni综合征联系起来.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 儿科上腺皮质癌 (ACC) 可能与Li-Fraumeni综合征 (LFS) 相关.
- 生殖系TP53突变是LFS的常见原因.
- 在一个儿科ACC患者中发现了TP53 c.758C>T (p.T253I) 突变.
研究的目的:
- 为了研究新型TP53 p.T253I突变的功能影响.
- 为了确定p.T253I突变是否与Li-Fraumeni综合征有关.
- 为了描述p.T253I变种的致病性.
主要方法:
- 稳定转导p53-/- HEK293细胞与野生类型 (WT) 或突变p53 (T253I,C176Y,R213X) 标记GFP.
- 对p53和MDM2蛋白水平的分析.
- 评估DNA损伤反应,DNA结合和交换能力.
主要成果:
- p.T253I突变导致p53蛋白水平增加和MDM2水平降低,表明调节受损.
- T253I p53表现出减少的DNA损伤反应能力.
- 与WT p53.3相比,T253I p53的DNA结合和交换能力下降被观察到.
结论:
- 这种TP53 p.T253I变种代表了一种致病突变.
- 这种突变会损害p53.3的关键瘤抑制功能.
- 这种p.T253I突变可能会使个体易患LFS相关的瘤.
相关概念视频
Abnormal Proliferation
5.1K
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...
5.1K
Cancer-Critical Genes II: Tumor Suppressor Genes
9.3K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K
Loss of Tumor Suppressor Gene Functions
5.8K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.8K
DNA Damage can Stall the Cell Cycle
9.9K
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...
9.9K
DNA Damage Can Stall the Cell Cycle
3.0K
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...
3.0K
Covalently Linked Protein Regulators
8.6K
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....
8.6K


