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Usp7 Regulates Hippo Pathway Through Deubiquitinating the Transcriptional Coactivator Yorkie

Overview
Journal Nat Commun
Specialty Biology
Date 2019 Jan 26
PMID 30679505
Citations 46
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Abstract

The Hippo pathway plays an important role in organ development and adult tissue homeostasis, and its deregulation has been implicated in many cancers. The Hippo signaling relies on a core kinase cascade culminating in phosphorylation of the transcription coactivator Yorkie (Yki). Although Yki is the key effector of Hippo pathway, the regulation of its protein stability is still unclear. Here, we show that Hippo pathway attenuates the binding of a ubiquitin-specific protease Usp7 to Yki, which regulates Hippo signaling through deubiquitinating Yki. Furthermore, the mammalian homolog of Usp7, HAUSP plays a conserved role in regulating Hippo pathway by modulating Yap ubiquitination and degradation. Finally, we find that the expression of HAUSP is positively correlated with that of Yap, both showing upregulated levels in clinical hepatocellular carcinoma (HCC) specimens. In summary, our findings demonstrate that Yki/Yap is stabilized by Usp7/HAUSP, and provide HAUSP as a potential therapeutic target for HCC.

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References
1.
Shen X, Sun X, Sun B, Li T, Wu G, Li Y . ARRDC3 suppresses colorectal cancer progression through destabilizing the oncoprotein YAP. FEBS Lett. 2018; 592(4):599-609. DOI: 10.1002/1873-3468.12986. View

2.
Ren F, Zhang L, Jiang J . Hippo signaling regulates Yorkie nuclear localization and activity through 14-3-3 dependent and independent mechanisms. Dev Biol. 2009; 337(2):303-12. PMC: 2812623. DOI: 10.1016/j.ydbio.2009.10.046. View

3.
Li W, Cooper J, Zhou L, Yang C, Erdjument-Bromage H, Zagzag D . Merlin/NF2 loss-driven tumorigenesis linked to CRL4(DCAF1)-mediated inhibition of the hippo pathway kinases Lats1 and 2 in the nucleus. Cancer Cell. 2014; 26(1):48-60. PMC: 4126592. DOI: 10.1016/j.ccr.2014.05.001. View

4.
Yimlamai D, Fowl B, Camargo F . Emerging evidence on the role of the Hippo/YAP pathway in liver physiology and cancer. J Hepatol. 2015; 63(6):1491-501. PMC: 4654680. DOI: 10.1016/j.jhep.2015.07.008. View

5.
Kagey J, Brown J, Moberg K . Regulation of Yorkie activity in Drosophila imaginal discs by the Hedgehog receptor gene patched. Mech Dev. 2012; 129(9-12):339-49. PMC: 3668547. DOI: 10.1016/j.mod.2012.05.007. View