KLF4 suppresses HDACi induced caspase activation and the SAPK pathway by targeting p57(Kip2).
Apoptosis
; 14(9): 1095-107, 2009 Sep.
Article
em En
| MEDLINE
| ID: mdl-19544095
ABSTRACT
Kruppel-like factor 4 (KLF4) belongs to a family of evolutionarily conserved zinc finger-containing transcription factors. It has been shown to mediate self renewal and pluripotency, regulate adipogenesis and play a critical role in monocyte differentiation. KLF4 is also highly expressed in squamous cell carcinomas and in 70% of all primary human breast cancers, suggesting a putative role for KLF4 as being an oncogene and as an antiapoptotic factor. However, the mechanism of this regulation remains unclear. Here, we show that KLF4 is induced during histone deacetylase inhibitor treatment, and regulates the extrinsic apoptosis pathway by inhibiting caspase cleavage. In addition, KLF4 binds to the p57(Kip2) promoter and transcriptionally upregulates its expression, which in turn inhibits the stress activated protein kinase cascade and c-Jun phosphorylation. Our findings indicate that in cancer cells that express high levels of KLF4 may be refractory to HDACi treatment. Results of our study demonstrate an unexpected antiapoptotic function of KLF4, and suggest an important cell fate determinant following histone deacetylase inhibitor induced apoptosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caspases
/
Proteínas Quinases Ativadas por Mitógeno
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Sistema de Sinalização das MAP Quinases
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Inibidor de Quinase Dependente de Ciclina p57
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Fatores de Transcrição Kruppel-Like
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Inibidores de Histona Desacetilases
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Ácidos Hidroxâmicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article