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Cell Rep. 2013 May 30;3(5):1663-77. doi: 10.1016/j.celrep.2013.04.020. Epub 2013 May 16.

The Ets transcription factor GABP is a component of the hippo pathway essential for growth and antioxidant defense.

Author information

1
State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiang'an District, Xiamen, Fujian 361102, China.

Abstract

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.

PMID:
23684612
PMCID:
PMC3855275
DOI:
10.1016/j.celrep.2013.04.020
[Indexed for MEDLINE]
Free PMC Article

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