Targeting HAUSP in both p53 wildtype and p53-mutant tumors.
Cell Cycle
; 17(7): 823-828, 2018.
Article
en En
| MEDLINE
| ID: mdl-29616860
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Proteasas
/
Regulación Neoplásica de la Expresión Génica
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Proteína p53 Supresora de Tumor
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Proteínas Proto-Oncogénicas c-mdm2
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Peptidasa Específica de Ubiquitina 7
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Cell Cycle
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos