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Targeting HAUSP in both p53 wildtype and p53-mutant tumors
| Content Provider | Scilit |
|---|---|
| Author | Tavana, Omid Sun, Hong Bin Gu, Wei |
| Copyright Year | 2018 |
| Description | Inhibition of Mdm2 function is a validated approach to restore p53 activity for cancer therapy; nevertheless, inhibitors of Mdm2 such as Nutlin-3 have certain limitations, suggesting that additional targets in this pathway need to be further elucidated. Our finding that the Herpesvirus-Associated Ubiquitin-Specific Protease (HAUSP, also called USP7) interacts with the p53/Mdm2 protein complex, was one of the first examples that deubiquitinases (DUBs) exhibit a specific role in regulating protein stability. Here, we show that inhibitors of HAUSP and Nutlin-3 can synergistically activate p53 function and induce p53-dependent apoptosis in human cancer cells. Notably, HAUSP can also target the N-Myc oncoprotein in a p53-independent manner. Moreover, newly synthesized HAUSP inhibitors are more potent than the commercially available inhibitors to suppress N-Myc activities in p53 mutant cells for growth suppression. Taken together, our study demonstrates the utility of HAUSP inhibitors to target cancers in both a p53-depdentent and -independent manner. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.1080/15384101.2018.1456293?needAccess=true https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056219/pdf |
| Ending Page | 828 |
| Page Count | 6 |
| Starting Page | 823 |
| ISSN | 15384101 |
| e-ISSN | 15514005 |
| DOI | 10.1080/15384101.2018.1456293 |
| Journal | Cell Cycle |
| Issue Number | 7 |
| Volume Number | 17 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2018-04-03 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cell Cycle Biochemistry and Molecular Biology Hausp Usp7 P53 Activation N-myc Cancer |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Developmental Biology Medicine Molecular Biology |
