Activation of the Interleukin-6 promoter by a dominant negative mutant of c-Jun.
Biochim Biophys Acta
; 1692(1): 17-24, 2004 May 28.
Article
en En
| MEDLINE
| ID: mdl-15158360
ABSTRACT
The human IL-6 promoter contains multiple regulatory elements such as those binding transcription factors belonging to the NF-kappaB (-75/-63), C/EBP (-158/-145 and -87/-76) and AP-1 (-283/-277) families. Herein, we report that ectopic expression of c-Jun, C/EBPdelta, and the p65 subunit of NF-kappaB synergistically activates an IL-6 promoter construct containing only a TATA box and a kappaB binding site. These results suggest that interactions among NF-kappaB, C/EBP, and AP-1, which are all activated by the most powerful physiological inducers of the IL-6 gene, namely TNF-alpha and IL-1, may be crucial for maximal activation of the IL-6 promoter in response to the two cytokines. Furthermore, we show that a mutated form of c-Jun lacking the transactivation domain (TAM-67) was a much stronger activator of the IL-6 promoter than c-Jun. In combination with p65 and/or C/EBPdelta, TAM-67 also synergistically activated the IL-6 promoter, while it inhibited TNF-alpha induced AP-1 activity directing an AP-1-responsive reporter plasmid. Lastly, electrophoretic mobility shift assay (EMSA) results strongly suggest the formation of complexes between p65, C/EBPdelta, and/or c-Jun or TAM-67 on the kappaB site, supporting the idea that the functional synergism is determined by a physical interaction. These data provide new insight into the molecular mechanisms regulating the formation of the transcription complex responsible for IL-6 promoter activation.
Buscar en Google
Bases de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Proteínas de Unión al Calcio
/
Interleucina-6
/
Regiones Promotoras Genéticas
/
Proteínas Proto-Oncogénicas c-jun
Límite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2004
Tipo del documento:
Article
País de afiliación:
Italia