Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha.
Journal:
EMBO J. 2001 DecAuthors:
Xiao G, Cvijic ME, Fong A, Harhaj EW, Uhlik MT, Waterfield M, Sun SC
Abstract
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
...[more]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.[less]
Mesh Headings:
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