Accelerated degradation of PML-retinoic acid receptor alpha (PML-RARA) oncoprotein by all-trans-retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway.
Cancer Res
; 56(13): 2945-8, 1996 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-8674046
ABSTRACT
Acute promyelocytic leukemia (APL) is associated with a chromosomal translocation t(15;17) and successfully differentiated by all-trans-retinoic acid (ATRA) in vivo as well as in vitro. The PML-retinoic acid receptor alpha (RARA) oncoprotein, which is generated by the translocation, blocks the differentiation, and ATRA is thought to modulate the dominant negative function of PML-RARA. However, the molecular effect of ATRA on PML-RARA is unknown. In this study, we showed by means of immunoblotting that the expression of PML-RARA decreased within 12 h in APL cells treated with ATRA at concentrations greater than 0.1 microM. The decrease of PML-RARA was associated with restoration of the normal subcellular PML localization. PML-RARA transcripts were not down-regulated by ATRA. However, lactacystin, a specific inhibitor of the proteasome, almost completely inhibited the decrease of PML-RARA. These data indicate that the PML-RARA degradation is accelerated by pharmacological concentrations of ATRA, suggesting that ATRA allows APL cells to differentiate by relieving the differentiation block.
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Banco de datos:
MEDLINE
Asunto principal:
Tretinoina
/
Cisteína Endopeptidasas
/
Proteínas Nucleares
/
Leucemia Promielocítica Aguda
/
Proteínas de Fusión Oncogénica
/
Proteínas de Neoplasias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Año:
1996
Tipo del documento:
Article
País de afiliación:
Japón