Knockdown of RCAN1.4 Increases Susceptibility to FAS-mediated and DNA-damage-induced Apoptosis by Upregulation of p53 Expression
The Korean Journal of Physiology and Pharmacology
;
: 483-489, 2009.
Artigo
em Inglês
| WPRIM
| ID: wpr-727453
ABSTRACT
Despite the potential importance of the human regulator of calcineurin 1 (RCAN-1) gene in the modulation of cell survival under stress, little is known about its role in death-inducing signal pathways. In this study, we addressed the effects of RCAN1.4 knockdown on cellular susceptibility to apoptosis and the activation of death pathway proteins. Transfection of siRNAs against RCAN1.4 resulted in enhanced Fas- and etoposide-induced apoptosis, which was associated with increased expression and translocation of Bax to mitochondria. Our results suggest that enhanced expression and activation of p53 was responsible for the upregulation of Bax and the increased sensitivity to apoptosis, which could be reversed by p53 knockdown. To explain the observed upregulation of p53, we propose a downregulation of the ubiquitin ligase HDM2, probably translationally. These findings show the importance of appropriate RCAN1.4 expression in the modulation of cell survival and reveal a link between RCAN1.4 and p53.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Carbonatos
/
Transfecção
/
Transdução de Sinais
/
Proteínas
/
Regulação para Baixo
/
Regulação para Cima
/
Sobrevivência Celular
/
Apoptose
/
Calcineurina
/
Ubiquitina
Limite:
Humanos
Idioma:
Inglês
Revista:
The Korean Journal of Physiology and Pharmacology
Ano de publicação:
2009
Tipo de documento:
Artigo
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