激活TP53的E3酶RNF144B是一种瘤抑制剂,可以防止基因组的不稳定
Etna Abad1, Jérémy Sandoz1, Gerard Romero1,2
1Department of Medicine and Life Sciences, Universidad Pompeu Fabra, Barcelona, 08003, Spain.
Journal of experimental & clinical cancer research : CR
|April 29, 2024
概括
通过保持基因组稳定性,RNF144B作为瘤抑制剂起作用. 它的缺乏促进癌细胞的增殖和治疗耐药性,突出其在癌症预防中的重要性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- TP53是一种关键的瘤抑制基因,在人类癌症中经常发生突变.
- RNF144B是一种E3泛素酶,已显示出瘤抑制活性,但其精确的作用和点在很大程度上仍未知.
- 这项研究研究了RNF144B在超出造血系统的人类癌症中的功能.
研究的目的:
- 为了阐明RNF144B在人类癌症中的瘤抑制作用.
- 为了确定RNF144B的分子点和作用机制.
- 评估RNF144B在癌症发展和患者预后中的临床相关性.
主要方法:
- 生成RNF144B缺乏细胞模型 (人类和小鼠,正常和癌症).
- 使用蛋白质组学,转录组学,体外/体内功能测试 (增殖,DNA修复,细胞循环,分裂).
- 分析了临床数据集并进行了生物信息学分析.
主要成果:
- 缺少RNF144B会增强细胞的增殖和转化,特别是在肺腺癌中.
- RNF144B调节参与细胞循环,DNA损伤反应和基因组稳定性的蛋白质降解.
- 丢失RNF144B与染色体不稳定性,线粒体缺陷,形积分和人类瘤的不良预后相关.
- 缺乏RNF144B的肺癌细胞对特定的化疗药物表现出耐药性.
结论:
- RNF144B是一种关键的瘤抑制剂,可以维持基因组的稳定性.
- RNF144B的功能对于预防癌症的发展和进展至关重要.
- 临床数据支持RNF144B在瘤抑制和患者结局中的作用.
相关概念视频
02:23Abnormal Proliferation
4.5K
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...
4.5K
01:23Negative Regulator Molecules
35.3K
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.
35.3K
02:37DNA Damage can Stall the Cell Cycle
9.1K
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...
9.1K
01:12Loss of Tumor Suppressor Gene Functions
4.8K
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...
4.8K
01:20The Retinoblastoma Gene
4.1K
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.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
7.4K
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...
7.4K