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

• Published in: Oncogene Vol. 20; no. 33; pp. 4484 - 4496
• Main Authors: NG, Patrick W. P, IHA, Hidekatsu, ZEICHNER, Steven L, IWANAGA, Yoichi, BITTNER, Michael, YIDONG CHEN, YUAN JIANG, GOODEN, Gerald, TRENT, Jeffrey M, MELTZER, Paul, JEANG, Kuan-Teh
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 27.07.2001; Nature Publishing Group
• Subjects: Apoptosis; Biological and medical sciences; Cell cycle; Cell lines; Cell physiology; Cytokines; DNA microarrays; DNA repair; Fundamental and applied biological sciences. Psychology; Genomes; Growth factors; human T-lymphotropic virus 1; Immunomodulation; Lymphocytes T; MAP kinase; mixed-lineage kinase; MLK-3 protein; Molecular and cellular biology; NF-κB protein; oncoproteins; Signal transduction; Tax protein; Transcription; Virus; DNA chip; Retroviridae; Activation; Transcription factor NFκB; Gene expression; Transcription factor; Genome; HTLV-I virus
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1204513

The Tax protein of human T-lymphotropic virus type 1 (HTLV-1), an oncoprotein that transactivates viral and cellular genes, plays a key role in HTLV-1 replication and pathogenesis. We used cDNA microarrays to examine Tax-mediated transcriptional changes in the human Jurkat T-cell lines JPX-9 and JPX-M which express Tax and Tax-mutant protein, respectively, under the control of an inducible promoter. Approximately 300 of the over 2000 genes examined were differentially expressed in the presence of Tax. These genes were grouped according to their function and are discussed in the context of existing findings in the literature. There was strong agreement between our results 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 modulators, 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-κB signaling. Our current results provide additional insights into Tax-mediated signaling.