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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


  • Xiao G
  • Cvijic ME
  • Fong A
  • Harhaj EW
  • Uhlik MT
  • Waterfield M
  • Sun SC


The EMBO journal

Publication Data

December 3, 2001

Associated Grants

  • Agency: NCI NIH HHS, Id: 1F32CA83280
  • Agency: NCI NIH HHS, Id: 2R01 CA68471

Mesh Terms

  • 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