Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein

Oncogene. 2000 Oct 26;19(45):5198-203. doi: 10.1038/sj.onc.1203894.

Abstract

Human T-cell leukemia virus type I (HTLV-I) Tax protein persistently stimulates the activity of IkappaB kinase (IKK), resulting in constitutive activation of the transcription factor NF-kappaB. Tax activation of IKK requires physical interaction of this viral protein with the IKK regulatory subunit, IKKgamma. The Tax/IKKgamma interaction allows Tax to engage the IKK catalytic subunits, IKKalpha and IKKbeta, although it remains unclear whether this linker function of IKKgamma is sufficient for supporting the Tax-specific IKK activation. To address this question, we have examined the sequences of IKKgamma required for modulating the Tax/IKK signaling. We demonstrate that when fused to Tax, a small N-terminal fragment of IKKgamma, containing its minimal IKKalpha/beta-binding domain, is sufficient for bringing Tax to and activating the IKK catalytic subunits. Disruption of the IKKalpha/beta-binding activity of this domain abolishes its function in modulating the Tax/IKK signaling. We further demonstrate that direct fusion of Tax to IKKalpha and IKKbeta leads to activation of these kinases. These findings suggest that the IKKgamma-directed Tax/IKK association serves as a molecular trigger for IKK activation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Enzyme Activation
  • Gene Products, tax / genetics
  • Gene Products, tax / metabolism*
  • Human T-lymphotropic virus 1*
  • I-kappa B Kinase
  • I-kappa B Proteins / metabolism
  • Protein Binding
  • Protein Subunits
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Recombinant Fusion Proteins / metabolism*
  • Signal Transduction

Substances

  • Gene Products, tax
  • I-kappa B Proteins
  • Protein Subunits
  • Recombinant Fusion Proteins
  • Protein-Serine-Threonine Kinases
  • I-kappa B Kinase