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Am J Physiol Gastrointest Liver Physiol 280: G669-G677, 2001;
0193-1857/01 $5.00
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Vol. 280, Issue 4, G669-G677, April 2001

Activation of NF-kappa B by hepatitis B virus X protein through an Ikappa B kinase-independent mechanism

Nicole H. Purcell*,1,2, Chenfei Yu*,1,2, Daoyao He*,2, Jialing Xiang1, Nir Paran3, Joseph A. DiDonato4, Shoji Yamaoka5, Yosef Shaul3, and Anning Lin1

1 Ben May Institute for Cancer Research, Committee on Cancer Biology, University of Chicago, Chicago, Illinois 60637; 2 Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294; 3 Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel; 4 Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195; and 5 Institute for Virus Research, Kyoto University, Kyoto 606, Japan

pX, the hepatitis B virus-encoded transcription coactivator, is involved in viral infection in vivo. pX stimulates the activity of several transcription factors including nuclear factor-kappa B (NF-kappa B), but the mechanism of activation is poorly understood. The Ikappa B kinase complex (IKK) mediates activation of NF-kappa B in response to various extracellular stimuli, including inflammatory cytokines like tumor necrosis factor and interleukin 1, human T cell lymphoma virus 1 Tax protein, and tumor promoters like phorbol esters. It is not known whether IKK also mediates activation of NF-kappa B by pX. Here we report that IKK was not essential for activation of NF-kappa B by pX. Expression of pX resulted in the degradation of Ikappa Balpha in the absence of its phosphorylation at Ser32 and Ser36 residues. Although pX stimulated the activity of cotransfected IKK-beta when it was overexpressed, it failed to activate endogenous IKK. Furthermore, expression of pX stimulated NF-kappa B nuclear translocation and transcriptional activity in IKK-gamma -null fibroblast 5R cells. Our data indicate that pX stimulates NF-kappa B activity through a mechanism that is dependent on Ikappa Balpha degradation but not on IKK activation.

nuclear factor-kappa B; inhibitor of nuclear factor-kappa B; X protein of hepatitis B virus

* N. H. Purcell, C. Yu, and D. He contributed equally to this work.




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