Jun blockade of erythropoiesis: role for repression of GATA-1 by HERP2.
Mol Cell Biol
; 24(17): 7779-94, 2004 Sep.
Article
en En
| MEDLINE
| ID: mdl-15314183
ABSTRACT
Although Jun upregulation and activation have been established as critical to oncogenesis, the relevant downstream pathways remain incompletely characterized. In this study, we found that c-Jun blocks erythroid differentiation in primary human hematopoietic progenitors and, correspondingly, that Jun factors block transcriptional activation by GATA-1, the central regulator of erythroid differentiation. Mutagenesis of c-Jun suggested that its repression of GATA-1 occurs through a transcriptional mechanism involving activation of downstream genes. We identified the hairy-enhancer-of-split-related factor HERP2 as a novel gene upregulated by c-Jun. HERP2 showed physical interaction with GATA-1 and repressed GATA-1 transcriptional activation. Furthermore, transduction of HERP2 into primary human hematopoietic progenitors inhibited erythroid differentiation. These results thus define a novel regulatory pathway linking the transcription factors c-Jun, HERP2, and GATA-1. Furthermore, these results establish a connection between the Notch signaling pathway, of which the HERP factors are a critical component, and the GATA family, which participates in programming of cellular differentiation.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Factores de Transcripción
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Células Madre Hematopoyéticas
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Regulación de la Expresión Génica
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Proteínas Proto-Oncogénicas c-jun
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Proteínas de Ciclo Celular
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Proteínas de Unión al ADN
/
Eritropoyesis
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Cell Biol
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos