Human T cell lymphotropic virus type I Tax protein trans-activates interleukin 15 gene transcription through an NF-κB site
Nazli Azimi,Keith A. Brown,Richard N. Bamford,Yutaka Tagaya,Ulrich Siebenlist,Thomas A. Waldmann +5 more
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TLDR
Evidence for trans-activation of the IL-15 gene by the HTLV-I Tax protein through an NF-κB motif is presented and a potential role for IL- 15 in HTLV -I-associated diseases such as adult T cell leukemia andHTLV- I-associated myopathy/tropical spastic paraparesis is suggested.Abstract:
Interleukin 15 (IL-15) mRNA is expressed in a wide variety of tissue types. However, with the exception of some T cell lines, IL-15 transcript expression has not been described in T cells. Herein we demonstrate that IL-15 mRNA can be detected in freshly isolated normal T cells and T cell lines. Furthermore, its expression is 3- to 4-fold higher in human T cell lymphotropic virus type I (HTLV-I)-infected T cells. By using reporter constructs bearing the 5′ regulatory region of the IL-15 gene, we observed a positive correlation between HTLV-I Tax protein expression and IL-15 promoter activity in HTLV-I-infected T cells. Additionally, by using a Jurkat T cell transfectant that expresses Tax under an inducible promoter, we demonstrated that the expression of IL-15 mRNA increased 3-fold as Tax was expressed, suggesting that the Tax protein activates IL-15 transcription. An NF-κB consensus sequence is located at the −75 and −65 region of the IL-15 5′ regulatory region. Mutations in the NF-κB motif or deletion of this sequence abrogated the promoter activity in both HTLV-I-positive and Jurkat Tax-transfectant cells. These data represent evidence for trans-activation of the IL-15 gene by the HTLV-I Tax protein through an NF-κB motif and suggest a potential role for IL-15 in HTLV-I-associated diseases such as adult T cell leukemia and HTLV-I-associated myopathy/tropical spastic paraparesis.read more
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Activators and target genes of Rel/NF-kappaB transcription factors.
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Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor
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