Endoplasmic reticulum stress induces G2 cell-cycle arrest via mRNA translation of the p53 isoform p53/47.
Mol Cell
; 38(1): 78-88, 2010 Apr 09.
Article
em En
| MEDLINE
| ID: mdl-20385091
ABSTRACT
p53 downstream pathways control G1 and G2 cell-cycle arrest, DNA repair, or apoptosis. However, it is still not clear how cells differentiate the cell-biological outcome of p53 activation in response to different types of stresses. The p53/47 isoform lacks the first 39 amino acids of full-length p53 including the Mdm2 binding site and the first trans-activation domain, and tetramers including p53/47 exhibit altered activity and biochemical properties. Here we show that endoplasmic reticulum stress promotes PERK-dependent induction of p53/47 mRNA translation and p53/47 homo-oligomerization. p53/47 induces 14-3-3sigma and G2 arrest but does not affect G1 progression. This is contrary to p53FL, which promotes G1 arrest but has no effect on the G2. These results show a unique role for p53/47 in the p53 pathway and illustrate how a cellular stress leads to a defined cell-biological outcome through expression of a p53 isoform.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
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Biossíntese de Proteínas
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RNA Mensageiro
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Fase G2
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Proteína Supressora de Tumor p53
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Isoformas de Proteínas
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Retículo Endoplasmático
Limite:
Humans
Idioma:
En
Revista:
Mol Cell
Ano de publicação:
2010
Tipo de documento:
Article