Stimulation of interleukin-13 expression by human T-cell leukemia virus type 1 oncoprotein Tax via a dually active promoter element responsive to NF-κB and NFAT
| Autor: | Katrin Silbermann, Ralph Grassmann, Grit Schneider |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Transcriptional Activation
T-Lymphocytes medicine.medical_treatment Biology Transactivation chemistry.chemical_compound Downregulation and upregulation Virology Cyclosporin a medicine Humans RNA Messenger Promoter Regions Genetic DNA Primers Human T-lymphotropic virus 1 Interleukin-13 NFATC Transcription Factors NF-kappa B Interleukin NFAT NF-κB Gene Products tax HTLV-I Infections TATA Box Cytokine Gene Expression Regulation chemistry Interleukin 13 Cancer research |
| Zdroj: | Journal of General Virology. 89:2788-2798 |
| ISSN: | 1465-2099 0022-1317 |
| DOI: | 10.1099/vir.0.2008/003699-0 |
| Popis: | The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein transforms human lymphocytes and is critical for the pathogenesis of HTLV-1-induced adult T-cell leukaemia. In HTLV-transformed cells, Tax upregulates interleukin (IL)-13, a cytokine with proliferative and anti-apoptotic functions that is linked to leukaemogenesis. Tax-stimulated IL-13 is thought to result in autocrine stimulation of HTLV-infected cells and thus may be relevant to their growth. The causal transactivation of theIL-13promoter by Tax is predominantly dependent on a nuclear factor of activated T cells (NFAT)-binding P element. Here, it was shown that the isolated IL-13 Tax-responsive element (IL13TaxRE) was sufficient to mediate IL-13 transactivation by Tax and NFAT1. However, cyclosporin A, a specific NFAT inhibitor, revealed that Tax transactivation of IL13TaxRE or wild-typeIL-13promoter was independent of NFAT and that NFAT did not contribute toIL-13upregulation in HTLV-transformed cells. By contrast, Tax stimulation was repressible by an efficient nuclear factor (NF)-κB inhibitor (IkBaDN), indicating the requirement for NF-κB. The capacity of NF-κB to stimulate IL13TaxRE was demonstrated by a strong response to NF-κB in reporter assays and by direct binding of NF-κB to IL13TaxRE. Thus, IL13TaxRE in theIL-13promoter represents a dually active promoter element responsive to NF-κB and NFAT. Together, these results indicate that Tax causes IL-13 upregulation in HTLV-1-infected cells via NF-κB. |
| Databáze: | OpenAIRE |
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