The Role of Tax Protein in the Regulation of IL-2 Production: Involvement of the c-Jun N Terminal Kinase

Abstract

The Tax protein of the HTLV-l retrovirus, which causes an aggressive form of T cell leukemia called adult T cell Leukemia (ATL), works via similar mechanisms as CD28 costimulation (the target sites are the same) to upregulate the expression of many cytokines known to be produced by infected cells. Some of these cytokines, particularly IL-2, are important for T cell proliferation and growth. Although it is not yet known how this contributes to the formation of leukemia, it is certain that Tax transactivation of cellular gene expression is important to its ability to transform cells. On the other hands, the all-trans-retinoic acid (ATRA) decreases JNK-1 activity, antagonizing the effect of the Tax protein in Jurkat Leukemia T cell transiently transfected for expressing the Tax protein. 

The decrease in JNK-1 activity was following for a marked decrease in the expression of IL-2 and IFN-g in Jurkat cells treated with ATRA in a doses-dependent manner suggesting a correlation between the expression of the JNK-1- and the activity of Tax protein.  The ATRA treatment was unable to decrease the expression of IL-4 and IL-10.  A luciferase assay using a well-known reporter gene expressing the IL-2 promoter or a tandem repeat of AP-1 or NF-B, demonstrated that both, AP-1 and NF-kB were affected by ATRA treatment.  In addition, our date showed that JNK-1 is constitutively activated in Jurkat Leukemia T cells expressing the Tax protein suggesting that JNK-1 is required for Tax induced proliferation of Jurkat leukemia cells.