The oncogene eIF4E reprograms the nuclear pore complex to promote mRNA export and oncogenic transformation.
Cell Rep
; 2(2): 207-15, 2012 Aug 30.
Article
en En
| MEDLINE
| ID: mdl-22902403
ABSTRACT
The eukaryotic translation initiation factor eIF4E is a potent oncogene that promotes the nuclear export and translation of specific transcripts. Here, we have discovered that eIF4E alters the cytoplasmic face of the nuclear pore complex (NPC), which leads to enhanced mRNA export of eIF4E target mRNAs. Specifically, eIF4E substantially reduces the major component of the cytoplasmic fibrils of the NPC, RanBP2, relocalizes an associated nucleoporin, Nup214, and elevates RanBP1 and the RNA export factors, Gle1 and DDX19. Genetic or pharmacological inhibition of eIF4E impedes these effects. RanBP2 overexpression specifically inhibits the eIF4E mRNA export pathway and impairs oncogenic transformation by eIF4E. The RanBP2 cytoplasmic fibrils most likely slow the release and/or recycling of critical export factors to the nucleus. eIF4E overcomes this inhibitory mechanism by indirectly reducing levels of RanBP2. More generally, these results suggest that reprogramming the NPC is a means by which oncogenes can harness the proliferative capacity of the cell.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
ARN Mensajero
/
Transformación Celular Neoplásica
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Proteínas Oncogénicas
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Poro Nuclear
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Factor 4E Eucariótico de Iniciación
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2012
Tipo del documento:
Article
País de afiliación:
Canadá