Genome-wide expression changes induced by HTLV-1 Tax: evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-kappa B activation

The Tax protein of human T-lymphotropic virus type 1 (HTLV-1), an oncoprote in that transactivates viral and cellular genes, plays a key role in HTLV-1 replication and pathogenesis. We used cDNA microarrays to examine Tax-medi ated transcriptional changes in the human Jurkat T-cell lines JPX-9 and JPX -M which express Tax and Tax-mutant protein, respectively, under the contro l of an inducible promoter. Approximately 300 of the over 2000 genes examin ed were differentially expressed in the presence of Tax. These genes were g rouped according to their function and are discussed in the context of exis ting findings in the literature. There was strong agreement between our res ults and genes previously reported as being Tax-responsive. Genes that were differentially expressed in the presence of Tax included those related to apoptosis, the cell cycle and DNA repair, signaling factors, immune modulat ors, cytokines and growth factors, and adhesion molecules. Functionally, we provide evidence that one of these genes, the mixed-lineage kinase MLK-3, is involved in Tax-mediated NF-kappaB signaling. Our current results provid e additional insights into Tax-mediated signaling.