The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense

• Main Authors: Hongtan Wu, Yubo Xiao, Shihao Zhang, Suyuan Ji, Luyao Wei, Fuqin Fan, Jing Geng, Jing Tian, Xiufeng Sun, Funiu Qin, Changnan Jin, Jianjun Lin, Zhen-Yu Yin, Ting Zhang, Lianzhong Luo, Yang Li, Siyang Song, Sheng-Cai Lin, Xianming Deng, Fernando Camargo, Joseph Avruch, Lanfen Chen, Dawang Zhou
• Format: Article
• Language: English
• Published: Elsevier 2013-05-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124713002027

The transcriptional coactivator Yes-associated protein (YAP) plays an important role in organ-size control and tumorigenesis. However, how Yap gene expression is regulated remains unknown. This study shows that the Ets family member GABP binds to the Yap promoter and activates YAP transcription. The depletion of GABP downregulates YAP, resulting in a G1/S cell-cycle block and increased cell death, both of which are substantially rescued by reconstituting YAP. GABP can be inactivated by oxidative mechanisms, and acetaminophen-induced glutathione depletion inhibits GABP transcriptional activity and depletes YAP. In contrast, activating YAP by deleting Mst1/Mst2 strongly protects against acetaminophen-induced liver injury. Similar to its effects on YAP, Hippo signaling inhibits GABP transcriptional activity through several mechanisms. In human liver cancers, enhanced YAP expression is correlated with increased nuclear expression of GABP. Therefore, we conclude that GABP is an activator of Yap gene expression and a potential therapeutic target for cancers driven by YAP.