Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Curr Biol. 2013 Feb 4;23(3):223-8. doi: 10.1016/j.cub.2012.11.061. Epub 2013 Jan 17.
The Hippo signaling pathway acts via the Yorkie (Yki)/Yes-associated protein (YAP) transcriptional coactivator family to control tissue growth in both Drosophila and mammals [1-3]. Yki/YAP drives tissue growth by activating target gene transcription, but how it does so remains unclear. Here we identify Mask as a novel cofactor for Yki/YAP. We show that Drosophila Mask forms a complex with Yki and its binding partner, Scalloped (Sd), on target-gene promoters and is essential for Yki to drive transcription of target genes and tissue growth. Furthermore, the stability and subcellular localization of both Mask and Yki is coregulated in response to various stimuli. Finally, Mask proteins are functionally conserved between Drosophila and humans and are coexpressed with YAP in a wide variety of human stem/progenitor cells and tumors.
Hippo 信号通路通过 Yorkie (Yki)/Yes 相关蛋白 (YAP) 转录共激活因子家族在果蝇和哺乳动物中控制组织生长[1-3]。Yki/YAP 通过激活靶基因转录来驱动组织生长，但具体机制尚不清楚。在这里，我们鉴定出 Mask 是 Yki/YAP 的一种新的共因子。我们发现果蝇 Mask 与 Yki 和其结合伴侣 Scalloped (Sd) 在靶基因启动子上形成复合物，对于 Yki 驱动靶基因转录和组织生长是必需的。此外，Mask 和 Yki 的稳定性和亚细胞定位都可以响应各种刺激进行协同调控。最后，果蝇和人类的 Mask 蛋白具有功能保守性，并且在广泛的人类干细胞/祖细胞和肿瘤中与 YAP 共表达。
