Reference - Detail
| RRC ID | 54432 |
|---|---|
| Author | Sun X, Ding Y, Zhan M, Li Y, Gao D, Wang G, Gao Y, Li Y, Wu S, Lu L, Liu Q, Zhou Z. |
| Title | Usp7 regulates Hippo pathway through deubiquitinating the transcriptional coactivator Yorkie. |
| Journal | Nat Commun |
| 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. |
| Volume | 10(1) |
| Pages | 411 |
| Published | 2019-1-24 |
| DOI | 10.1038/s41467-019-08334-7 |
| PII | 10.1038/s41467-019-08334-7 |
| PMID | 30679505 |
| PMC | PMC6345853 |
| MeSH | Animals Carcinoma, Hepatocellular / metabolism DNA-Binding Proteins / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Gene Expression Profiling Gene Expression Regulation Gene Knockdown Techniques Hedgehog Proteins / metabolism Intracellular Signaling Peptides and Proteins / metabolism* Liver Neoplasms / metabolism Nuclear Proteins / genetics Nuclear Proteins / metabolism* Protein Binding Protein Processing, Post-Translational* Protein Serine-Threonine Kinases / metabolism* Signal Transduction Trans-Activators / genetics Trans-Activators / metabolism* Transcription Factors / metabolism* Ubiquitin-Specific Peptidase 7 / genetics Ubiquitin-Specific Peptidase 7 / metabolism* Ubiquitination Up-Regulation YAP-Signaling Proteins |
| IF | 11.878 |
| Times Cited | 12 |
| Resource | |
| Drosophila | |