The Levels of MDM2 Protein Are Decreased by a Proteasome-Mediated Proteolysis Prior to Caspase-3-Dependent pRb and PARP Cleavages
Journal of Korean Medical Science
;
: 135-139, 2001.
Artículo
en Inglés
| WPRIM
| ID: wpr-179362
ABSTRACT
MDM2 is a substrate of caspase-3 in p53-mediated apoptosis. In addition, MDM2 mediates its own ubiquitination in a RING finger-dependent manner. Thus, we investigated whether MDM2 is degraded through a ubiquitin-dependent proteasome pathway in the absence of p53. When HL-60 cells, p53 null, were treated with etoposide, MDM2 was markedly decreased prior to caspase-3-dependent retinoblastoma tumor suppressor protein (pRb) and poly (ADP- ribose) polymerase (PARP) cleavages. Moreover, down-regulation of MDM2 level was not coupled with its mRNA down-regulation. However, the level of MDM2 was partially restored by proteasome inhibitors such as LLnL and lactacystin, even in the presence of etoposide. Our results suggest that, in the p53 null status, MDM2 protein level is decreased by proteasome-mediated proteolysis prior to caspase-3-dependent PARP and pRb cleavages.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Cisteína Endopeptidasas
/
Regulación hacia Abajo
/
Proteína de Retinoblastoma
/
Proteínas Proto-Oncogénicas
/
ADP Ribosa Transferasas
/
Apoptosis
/
Células HL-60
/
Caspasas
/
Etopósido
/
Complejos Multienzimáticos
Límite:
Humanos
Idioma:
Inglés
Revista:
Journal of Korean Medical Science
Año:
2001
Tipo del documento:
Artículo
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