title: Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha.
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 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.
authors.affiliation: Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: G
authors.initials: G
authors.lastname: Xiao
authors.forename: M E
authors.initials: ME
authors.lastname: Cvijic
authors.forename: A
authors.initials: A
authors.lastname: Fong
authors.forename: E W
authors.initials: EW
authors.lastname: Harhaj
authors.forename: M T
authors.initials: MT
authors.lastname: Uhlik
authors.forename: M
authors.initials: M
authors.lastname: Waterfield
authors.forename: S C
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D004789:Enzyme Activation; D016356:Gene Products, tax / Q000378:metabolism*; D005799:Genes, Dominant; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase; D015151:Immunoblotting; D019169:Jurkat Cells; D008156:Luciferases / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism
chemical_list: D016356:Gene Products, tax; D008164:Luminescent Proteins; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D025801:Ubiquitin; D014759:Viral Envelope Proteins; D049452:Green Fluorescent Proteins; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human