核氨基酸信号传递促进乳腺癌中YAP/TAZ-TEAD转录活性
Oisun Jung1,2, Min-Jeong Baek1,2,3, Colin Wooldrik1,2,3
1Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
核类化物,如PI{4,5) P2和PI{3,4,5) P3,作为YAP/TAZ-TEAD复合体结合的辅因子. 抑制这些氨酸化物会降低乳腺癌细胞的运动性和YAP/TAZ基因表达.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 河马通路效应者是与YAP相关的蛋白1 (YAP) 和TAZ是转录的协同激活剂.
- YAP/TAZ-TEAD复合体驱动癌症特定的转录程序,促进瘤的进展,特别是在乳腺癌中.
- 针对YAP/TAZ-TEAD复合体的目标是具有挑战性的,因为我们对其机制的理解并不完整.
研究的目的:
- 为了阐明YAP/TAZ-TEAD复合体形成的机制.
- 为了确定参与YAP/TAZ-TEAD复杂功能中的新型共因子.
- 探索YAP/TAZ驱动的乳腺癌中的潜在治疗点.
主要方法:
- 研究了核胺酸在中介YAP/TAZ-TEAD结合中的作用.
- 使用的酸酸酶 (PIPKIα,IPMK) 和它们的产物 (PI(4,5) P2,PI(3,4,5) P3).
- 评估了抑制激酶或氨酸酸化合物对YAP/TAZ-TEAD相互作用,基因表达和细胞运动性的影响.
主要成果:
- 核氨酸,特别是PI{4,5) P2和PI{3,4,5) P3,作为关键的辅助因子,将YAP/TAZ与TEAD相连接.
- 酸酸酶的抑制或与这些脂质的YAP/TAZ关联减弱了YAP/TAZ-TEAD相互作用.
- 这种抑制还降低了YAP/TAZ基因表达和乳腺癌细胞运动率.
结论:
- 核酸信号传递是YAP/TAZ活动的以前未知的调节器.
- 鉴定到的氨酸介导机制为YAP/TAZ驱动的乳腺癌提供了潜在的治疗策略.
- 需要对伊诺西酸盐的作用进行进一步的研究.
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
06:54Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
TGF - β Signaling Pathway
The JAK-STAT Signaling Pathway
MAPK Signaling Cascades
