Volume 8 Supplement 1

15th International Conference on Human Retroviruses: HTLV and Related Viruses

Open Access

IKKepsilon involvement in Tax-mediated activation of INF pathway

  • Giorgia Cremonese1Email author,
  • Francesca Avesani1,
  • Erica Diani1,
  • Marco Turci1,
  • Gianfranco Di Gennaro1,
  • Umberto Bertazzoni1 and
  • Maria G Romanelli1
Retrovirology20118(Suppl 1):A137

https://doi.org/10.1186/1742-4690-8-S1-A137

Published: 6 June 2011

HTLV-1 Tax de-regulates several cellular signaling pathways leading to cell transformation by altering gene expression, intracellular protein distribution and cell proliferation. Tax-1 induces persistent activation of several transcriptional factors and signal transduction pathways, including NF-κB and CREB/ATF. It is known that Tax-1 constitutively activates TAK1 (transforming growth factor-β-activated kinase 1) and modifies the interferon (INF) regulatory signals by controlling the expression of INF transcription factors 3 (INF3) and INF4. We have recently reported that HTLV-1 and HTLV-2 Tax proteins interact with TAK1-binding protein 2 (TAB2) of the NF-κB pathway and that both Tax proteins transactivate NF-κB promoters [1]. TAB2 functions as an adaptor protein to recruit TAK1 to TRAF2 (TNF-α receptor-associated factor) in TNF-α signaling pathways.

In the present study we have investigated Tax-1 and Tax-2 role in modifying INF and NF-κB activation through the recruitment of IKKepsilon, an IκB kinase homologue involved in NF-κB and INF3 signaling pathways. By co-immunoprecipitation experiments, we have found that both IKKepsilon and Tax-1, but not Tax-2, are present in protein complexes in transfected cells. IKKepsilon and Tax-1 or Tax-2 role in the activation of INF responsive elements or NF-κB containing promoters have been analyzed after transfecting the protein genes in 293T cells and measuring the effect by luciferase assay. Co-expression of Tax-1 and IKKepsilon resulted in an increased IRF activation mediated by IKKepsilon. Interaction of IKKepsilon with Tax-1 and Tax-2 and their possible effects in the de-regulation of the IRF3 pathways will be discussed.

Authors’ Affiliations

(1)
Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona

References

  1. Avesani F, Romanelli MG, Turci M, Di Gennaro G, Sampaio C, Bidoia C, Bertazzoni U, Bex F: Association of HTLV Tax proteins with TAK1 binding protein 2 and RelA in calreticulin containing cytoplasmic structures participates in Tax-mediated NF κB activation. Virology. 2010, 408: 39-48. 10.1016/j.virol.2010.08.023.View ArticlePubMedGoogle Scholar

Copyright

© Cremonese et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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