替代Wnt信号激活了YAP/TAZ
Hyun Woo Park1, Young Chul Kim2, Bo Yu3
1Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
Cell
|August 16, 2015
概括
转录共激活剂YAP和TAZ是器官大小和组织平衡的关键调节剂,它们的失调有助于人类的癌症. 在这里,我们发现YAP/TAZ作为替代Wnt信号通道的真实下游效应器. Wnt5a/b和Wnt3a诱导了独立于正规Wnt/β-catenin信号的YAP/TAZ激活. 在机理上,我们划出了由Wnt-FZD/ROR-Gα12/13-Rho GTPases-Lats1/2组成的"替代Wnt-YAP/TAZ信号轴",以促进YAP/TAZ激活和TEAD介导的转录. YAP/TAZ调解了替代Wnt信号的生物功能,包括基因表达,骨质分化,细胞迁移和Wnt/β-catenin信号的对抗作用. 我们的合作使YAP/TAZ成为替代Wnt信号的关键媒介.
科学领域:
- 细胞生物学
- 分子生物学
- 癌症研究
背景情况:
- 转录共激活剂YAP和TAZ调节器官大小和组织平衡.
- 对YAP/TAZ的失调与人类的癌症有关.
- 替代Wnt信号通路在细胞过程中起着至关重要的作用.
研究的目的:
- 确定替代Wnt信号通路的下游效应器.
- 阐明替代Wnt信号激活YAP/TAZ的机制.
- 建立 YAP/TAZ 作为替代 Wnt 信号功能的媒介.
主要方法:
- 研究了YAP/TAZ对Wnt5a/b和Wnt3a的反应作用.
- 从Wnt连接体到YAP/TAZ激活的信号级联.
- 评估YAP/TAZ介导的功能,包括基因表达和细胞分化.
主要成果:
- YAP/TAZ是另类Wnt信号的真实下游效应器.
- Wnt5a/b和Wnt3a可以独立于规范的Wnt/β-catenin信号来激活YAP/TAZ.
- 识别的信号轴包括Wnt-FZD/ROR-Gα12/13-Rho GTPases-Lats1/2.
结论:
- YAP/TAZ调解了替代Wnt信号的关键生物功能.
- 替代Wnt信号促进了YAP/TAZ激活和TEAD介导的转录.
- YAP/TAZ是替代Wnt信号的关键媒介,影响基因表达,分化和细胞迁移.
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