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NF-κB activation by the viral oncoprotein StpC is enhanced by ERK-mediated p52 and RelB upregulation

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Induction of T-cell lymphomas and T-cell growth transformation by Herpesvirus saimiri strain C-488 depend on the saimiri transformation-associated protein of subgroup C (StpC). Previous studies identified the transcription factor NF-κB as the major cellular target of StpC. NF-κB activation relies on a TRAF binding motif in StpC and was enhanced by coexpression of constitutively active Ras or Raf. Concomitantly, StpC repressed Ras-mediated ERK and AP-1 activation. Nevertheless, we now found that specific inhibitors of MEK as well as ERK abrogated cooperative NF-κB activation. Triggering the ERK pathway by external stimuli, e.g. PMA, also enhanced StpC-induced NF-κB activity, however, with a significant delay relative to ERK1/2 phosphorylation. These observations suggested that ERK activity regulates the expression of proteins limiting StpC's capacity to induce NF-κB. Westernblot analyses of proteins representing the classical and alternative pathways of NF-κB activation revealed that StpC cooperates with Ras and even more with PMA to upregulate the expression and nuclear localization of RelB and NF-κB2/p52; furthermore, StpC coimmunoprecipitated TRAF2, but not TRAF6, Ras or Raf. In summary, these data suggest that ERK-inducing signaling pathways support NF-κB activation by StpC through an enhanced expression of NF-κB proteins utilized by the alternative pathway, which is triggered by StpC:TRAF2 complexes. Future studies will have to address the relevance of the enhancing effect for the proliferation of Herpesvirus saimiri-transformed human T lymphocytes.

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Correspondence to K Katsch.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://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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Katsch, K., Glanz, A., Richter, S. et al. NF-κB activation by the viral oncoprotein StpC is enhanced by ERK-mediated p52 and RelB upregulation. Cell Commun Signal 7, A50 (2009) doi:10.1186/1478-811X-7-S1-A50

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Keywords

  • Alternative Pathway
  • Binding Motif
  • Viral Oncoprotein
  • Growth Transformation
  • Herpesvirus Saimiri