Tip60是一种需要用于基因诱导的DNA损伤反应的哈普洛不足瘤抑制剂
Chiara Gorrini1, Massimo Squatrito, Chiara Luise
1Department of Experimental Oncology, European Institute of Oncology (IEO), IFOM-IEO Campus, Milan 20139, Italy.
Nature
|August 31, 2007
概括
乙转移酶Tip60通过抵消Myc诱导的淋巴发育而起瘤抑制作用. 在早期瘤阶段,Tip60的Haplo-insufficiency会损害DNA损伤反应 (DDR),与p53突变产生协同作用.
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:
- Tip60是一种乙转移酶,通过调节Myc和p53.3等转录因子来影响瘤发生.
- Tip60调节DNA损伤响应 (DDR) 信号传输,当被瘤基因触发时,可以抵消瘤进展.
研究的目的:
- 为了研究Tip60在Myc诱导的淋巴发育中的作用,使用单 haplo不足的小鼠模型.
- 确定Tip60的瘤抑制活性是否与其在DDR和ARF-p53通路中的功能有关.
主要方法:
- 使用了对Tip60淘汰等位基因异构的转基因小鼠E(mu) -myc (Tip60+/-).
- 评估了Myc诱导的淋巴发育,DDR,转录,增殖和ARF-p53通路.
- 分析了TIP60基因变异和蛋白质表达的人类淋巴瘤和癌症.
主要成果:
- 在前瘤或早期瘤阶段,Tip60异性 (Tip60+/-) 抵消了Myc诱导的淋巴发育,以平分不足的方式.
- Tip60异性损害了Myc诱导的DDR,但并没有导致B细胞的一般DDR缺陷.
- 人类TIP60 (HTATIP) 在淋巴瘤和癌症中经常出现单基因损失,与疾病级别和p53突变相关.
结论:
- 在小鼠和人类中,Tip60表现出平分不充分的瘤抑制活性,独立于它在ARF-p53通路中的作用.
- 足够的Tip60水平对于在初始瘤细胞中安装瘤基因诱导的DDR至关重要.
- 由于Tip60缺乏症导致的DDR失败可能与p53突变协同促进瘤进展.
相关概念视频
00:59Gene Therapy
Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be inserted. The...
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...
01:12Loss of Tumor Suppressor Gene Functions
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...
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
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...