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

Patrick W.P. Ng, Hidekatsu Iha, Yoichi Iwanaga, Michael Bittner, Yidong Chen, Yuan Jiang, Gerald Gooden, Jeffrey M. Trent, Paul Meltzer, Kuan Teh Jeang, Steven L. Zeichner

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4484-4496
Number of pages13
JournalOncogene
Volume20
Issue number33
DOIs
StatePublished - Jul 27 2001
Externally publishedYes

Keywords

  • Gene expression
  • HTLV-1
  • JPX-9
  • MLK-3
  • Microarray
  • Tax

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Ng, P. W. P., Iha, H., Iwanaga, Y., Bittner, M., Chen, Y., Jiang, Y., Gooden, G., Trent, J. M., Meltzer, P., Jeang, K. T., & Zeichner, S. L. (2001). Genome-wide expression changes induced by HTLV-1 Tax: Evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-κB activation. Oncogene, 20(33), 4484-4496. https://doi.org/10.1038/sj.onc.1204513