C端融合伙伴活动有助于YAP1::TFE3的致癌功能
Patrick J Cimino1, Dylan J Keiser2, Abigail G Parrish3
1Neuropathology Unit, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA.
导致YAP1基因的融合, TFE3的融合合作伙伴
科学领域:
- 癌症学
- 分子生物学
- 癌症遗传学
背景情况:
- YAP1基因融合是许多人类癌症的关键驱动因素.
- YAP1融合蛋白激活了TEAD依赖的致癌途径.
- 在YAP1瘤发生过程中,C端融合伙伴的作用尚不清楚.
研究的目的:
- 调查TFE3融合伙伴领域对YAP1::TFE3致癌活性的贡献.
- 分析TFE3DNA结合和激活域对瘤形成和特征的影响.
主要方法:
- 产生和体内表达八种不同的YAP1基因融合,包括YAP1::TFE3.
- 在TFE3域 (LZ,bHLH,AD) 中产生YAP1::TFE3突变变体.
- 在体外和体内功能测试以评估致癌活性和瘤发展.
主要成果:
- 与其他YAP1融合相比,TFE3诱导了不同的瘤组织形态.
- 在体外,TFE3 DNA结合域突变降低了TFE3活性,但增加了YAP1活性.
- 在体内,TFE3域缺失改变了瘤特征,TFE3激活域的丧失取消了瘤的形成.
结论:
- TFE3融合伙伴域显著影响YAP1::TFE3的致癌功能.
- 特定的TFE3域在YAP1::TFE3驱动的瘤启动和进展中发挥关键作用.
更多相关视频
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
09:58Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
相关概念视频
Induced Pluripotent Stem Cells
Somatic...
TGF - β Signaling Pathway
Cancer-Critical Genes I: Proto-oncogenes
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...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Eukaryotic Transcription Activators
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
Cytoskeletal Accessory Proteins
