HIV1-tat increases cooperation between AP1 and NFAT transcription factors at DNA composite response elements.
Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. TuOrA1137)
Hidalgo-Estevez AM, Gonzalez E, Punzon C, Fresno M University, Madrid, Spain
Alteration of cellular gene expression is one of the mechanisms involved in the inmune dysregulation induced upon HIV infection. In this regard, the HIV1-tat protein has been shown to affect the activation of different cellular transcription factors through direct and indirect mechanisms. We have investigated the role of tat on NFAT and AP1 transcription factors that, independently or through cooperative interactions, regulate the expression of multiple cytokine genes. Both constitutive and transient tat expression in jurkat T cells was able to strongly enhance cooperative NFAT/AP1 dependent transcription induced by T cell activating stimuli as phorbol esters plus calcium ionophore without significantly altering transactivation dependent on pure AP1 or NF-kappaB response elements. This tat efect was independent on the ability of tat to transactivate HIV LTR. Moreover transactivation of NFAT/AP1 dependent reporter by transfection of NFAT and c-jun was strongly enhanced 100 fold by simultaneous tat transfection. More interestingly, the expression of tat increased the amount of NFAT/AP1 complexes bound to the NFAT/AP1 site of the IL-2 promoter without significantly altering independent binding of NFAT and AP1 to their corresponding oligonucleotide probes. HIV1-tat was co-immunoprecipitated with NFAT1. Furthermore, addition of recombinant tat to nuclear extracts from normal activated jurkat cells also increased NFAT/AP1 binding to the probe. Moreover, GST-tat eliminates this binding and the use of deletion mutants indicate that the region involved may include aa 28-48. These results indicate that intracellular tat is able to interact with NFAT, affecting its functional cooperation without altering neither independent binding of these transcription factors to DNA nor AP1 dependent transactivation.
Keywords: AEGIS, Gene Products, tat, Response Elements, Transcription Factors, Genes, tat, Transcription Factor AP-1, HIV-1, DNA, Trans-Activation (Genetics), DNA-Binding Proteins, Transcription, Genetic, Promoter Regions (Genetics), NF-kappa B, Proto-Oncogene Proteins c-jun, Jurkat Cells, Interleukin-2, T-Lymphocytes, Gene Expression, Protein Binding, NF-kappa B p65, Humans, genetics
