PRIMA-1(MET) induces nucleolar accumulation of mutant p53 and PML nuclear body-associated proteins.
Oncogene
; 26(7): 982-92, 2007 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-16909106
ABSTRACT
We have previously identified PRIMA-1, a low molecular weight compound that restores the transcriptional transactivation function to mutant p53 and induction of apoptosis. To explore the molecular mechanism for PRIMA-1-induced mutant p53-dependent apoptosis, we examined the intracellular distribution of mutant p53 upon treatment with PRIMA-1(MET) by immunofluorescence staining. We found that PRIMA-1(MET) induced nucleolar translocation of mutant p53 and the promyelocytic leukemia (PML) nuclear body-associated proteins PML, CBP and Hsp70. Levels of Hsp70 were significantly enhanced by PRIMA-1(MET) treatment. PRIMA-Dead, a compound structurally related to PRIMA-1 but unable to induce mutant p53-dependent apoptosis, failed to induce nucleolar translocation of mutant p53. Our results suggest that redistribution of mutant p53 to nucleoli plays a role in PRIMA-1-induced apoptosis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Aza
/
Fatores de Transcrição
/
Proteínas Nucleares
/
Nucléolo Celular
/
Proteína Supressora de Tumor p53
/
Compostos Bicíclicos Heterocíclicos com Pontes
/
Proteínas Supressoras de Tumor
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Suécia