Proteasome inhibitors suppress MYB oncogenic activity in a p300-dependent manner.
Cancer Lett
; 520: 132-142, 2021 11 01.
Article
en En
| MEDLINE
| ID: mdl-34256093
Studies of the role of MYB in human malignancies have highlighted MYB as a potential drug target for acute myeloid leukemia (AML) and adenoid cystic carcinoma (ACC). Although transcription factors are often considered un-druggable, recent work has demonstrated successful targeting of MYB by low molecular weight compounds. This has fueled the notion that inhibition of MYB has potential as a therapeutic approach against MYB-driven malignancies. Here, we have used a MYB reporter cell line to screen a library of FDA-approved drugs for novel MYB inhibitors. We demonstrate that proteasome inhibitors have significant MYB-inhibitory activity, prompting us to characterize the proteasome inhibitor oprozomib in more detail. Oprozomib was shown to interfere with the ability of the co-activator p300 to stimulate MYB activity and to exert anti-proliferative effects on human AML and ACC cells. Overall, our work demonstrated suppression of oncogenic MYB activity as a novel result of proteasome inhibition.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Carcinoma Adenoide Quístico
/
Proteínas Proto-Oncogénicas c-myb
/
Proteína p300 Asociada a E1A
Límite:
Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Irlanda