Novel NFAT sites that mediate activation of the interleukin-2 promoter in response to T-cell receptor stimulation.
Mol Cell Biol
; 15(11): 6299-310, 1995 Nov.
Article
en En
| MEDLINE
| ID: mdl-7565783
ABSTRACT
The transcription factors NFAT and AP-1 have been shown to be essential for inducible interleukin-2 (IL-2) expression in activated T cells. NFAT has been previously reported to bind to two sites in the IL-2 promoter in association with AP-1 at the distal antigen response element at -280 and at -135. On the basis of DNase I footprinting with recombinant NFAT and AP-1 proteins, gel shift assays, and transfection experiments, we have identified three additional NFAT sites in the IL-2 promoter. Strikingly, all five NFAT sites are essential for the full induction of promoter activity in response to T-cell receptor stimulation. Four of the five NFAT sites are part of composite elements able to bind AP-1 in association with NFAT. These sites display a diverse range of cooperativity and interdependency on NFAT and AP-1 proteins for binding. One of the NFAT sites directly overlaps the CD28-responsive element. We present evidence that CD28 inducibility is conferred by the AP-1 component in NFAT-AP-1 composite elements. These findings provide further insight into the mechanisms involved in the regulation of the IL-2 promoter.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Proteínas Nucleares
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Receptores de Antígenos de Linfocitos T
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Interleucina-2
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Regiones Promotoras Genéticas
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Factor de Transcripción AP-1
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Células TH1
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Proteínas de Unión al ADN
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
1995
Tipo del documento:
Article