AKT mediates actinomycin D-induced p53 expression.
Oncotarget
; 5(3): 693-703, 2014 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-24525337
ABSTRACT
At high cytotoxic concentrations, actinomycin D (ActD) blocks transcription, decreasing levels of MDM2 and thus causing p53 stabilization. At low cytostatic concentrations, ActD causes ribosomal stress, which decreases MDM2 activity, resulting in p53 stabilization and activation. ActD can thus be used for p53-based cyclotherapy. We analyzed pathways mediating ActD-induced p53 expression. Inhibitors (LY294002, wortmannin, and deguelin) of phosphatidylinositol 3-kinases (PI3K) and AKT, but not inhibitors of MEK1/2, JNK, and p38-MAPK abolished the ActD-induced p53 expression in diverse cell types. RNA interference further supported these results. When AKT was downregulated by small hairpin RNA-AKTs, ActD-induced p53 expression was significantly decreased. ActD caused AKT phosphorylation at Ser473, indicating full activation of AKT. The potential for cancer therapy is discussed.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteína p53 Supresora de Tumor
/
Dactinomicina
/
Proteínas Proto-Oncogénicas c-akt
Límite:
Humans
Idioma:
En
Revista:
Oncotarget
Año:
2014
Tipo del documento:
Article