Journal
CELL REPORTS
Volume 3, Issue 5, Pages 1663-1677Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2013.04.020
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Funding
- China's 1000 Young Talents Program
- 111 Project of the Ministration of Education of China [B06016]
- Fundamental Research Funds for the Central Universities of China [2010111079]
- National Natural Science Foundation of China [81101503/H1602, 31270918/C080101, 81222030/H1602]
- Natural Science Foundation of Fujian [2011J05096]
- Program of Introducing Talents of Discipline to Universities [B12001]
- ROI awards [CA136567, DK17776]
- DOD award [W81XWH-09-NFRP-NIA]
- Stand Up to Cancer
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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.
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