Usp7 Regulates Hippo Pathway Through Deubiquitinating the Transcriptional Coactivator Yorkie
Overview
Authors
Affiliations
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.
The Role of Yes-Associated Protein in Inflammatory Diseases and Cancer.
Zhong B, Du J, Liu F, Sun S MedComm (2020). 2025; 6(3):e70128.
PMID: 40066231 PMC: 11892025. DOI: 10.1002/mco2.70128.
Tai/NCOA2 suppresses the Hedgehog pathway by directly targeting the transcription factor Ci/GLI.
Yu X, Wang X, Ma K, Gao D, Deng Y, Zhou D Proc Natl Acad Sci U S A. 2024; 121(47):e2409380121.
PMID: 39531503 PMC: 11588115. DOI: 10.1073/pnas.2409380121.
upregulated by promotes ferroptosis via inhibiting axis in sepsis-induced acute lung injury.
Lv H, Yu J, Qian X, Shu J, Qian Q, Shen L iScience. 2024; 27(6):109667.
PMID: 38966570 PMC: 11223090. DOI: 10.1016/j.isci.2024.109667.
The AAA-ATPase Ter94 regulates wing size in Drosophila by suppressing the Hippo pathway.
Li M, Ding W, Deng Y, Zhao Y, Liu Q, Zhou Z Commun Biol. 2024; 7(1):533.
PMID: 38710747 PMC: 11074327. DOI: 10.1038/s42003-024-06246-x.
SPOP point mutations regulate substrate preference and affect its function.
Deng Y, Ding W, Ma K, Zhan M, Sun L, Zhou Z Cell Death Dis. 2024; 15(2):172.
PMID: 38409107 PMC: 10897488. DOI: 10.1038/s41419-024-06565-1.