Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha.
IkappaB kinase (IKK) is a key mediator of NF-kappaB activation induced by various immunological signals. In T cells and most other cell types, the primary target of IKK is a labile inhibitor of NF-kappaB, IkappaBalpha, which is responsible for the canonical NF-kappaB activation. Here, we show that in T cells infected with the human T-cell leukemia virus (HTLV), IKKalpha is targeted to a novel signaling pathway that mediates processing of the nfkappab2 precursor protein p100, resulting in active production of the NF-kappaB subunit, p52. This pathogenic action is mediated by the HTLV-encoded oncoprotein Tax, which appears to act by physically recruiting IKKalpha to p100, triggering phosphorylation-dependent ubiquitylation and processing of p100. These findings suggest a novel mechanism by which Tax modulates the NF-kappaB signaling pathway.
Pubmed ID: 11726516 RIS Download
Amino Acid Sequence | Cell Line | Enzyme Activation | Gene Products, tax | Genes, Dominant | Genes, Reporter | Green Fluorescent Proteins | Human T-lymphotropic virus 1 | Humans | I-kappa B Kinase | Immunoblotting | Jurkat Cells | Luciferases | Luminescent Proteins | Molecular Sequence Data | NF-kappa B | NF-kappa B p52 Subunit | Phosphorylation | Plasmids | Protein Binding | Protein Structure, Tertiary | Protein-Serine-Threonine Kinases | Retroviridae | Signal Transduction | T-Lymphocytes | Time Factors | Transfection | Ubiquitin | Viral Envelope Proteins