Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha

• Published in: The EMBO journal 2001-12, Vol.20 (23), p.6805-6815
• Main Authors: Xiao, G, Cvijic, M E, Fong, A, Harhaj, E W, Uhlik, M T, Waterfield, M, Sun, S C
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Cell Line; Enzyme Activation; Gene Products, tax - metabolism; Genes, Dominant; Genes, Reporter; Green Fluorescent Proteins; Human T-lymphotropic virus 1 - metabolism; Humans; I-kappa B Kinase; Immunoblotting; Jurkat Cells; Luciferases - metabolism; Luminescent Proteins - metabolism; Molecular Sequence Data; NF-kappa B - metabolism; NF-kappa B p52 Subunit; Phosphorylation; Plasmids - metabolism; Protein Binding; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases - metabolism; Retroviridae - genetics; Retroviridae - metabolism; Signal Transduction; T-Lymphocytes - metabolism; Time Factors; Transfection; Ubiquitin - metabolism; Viral Envelope Proteins - metabolism
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/20.23.6805

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.