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.
Xiao
G
G
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Cvijic
M E
ME
Fong
A
A
Harhaj
E W
EW
Uhlik
M T
MT
Waterfield
M
M
Sun
S C
SC
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
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