Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein.
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.
Xiao
G
G
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania, PA 17033, USA.
Sun
S C
SC
D001665:Binding Sites; D004789:Enzyme Activation; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D015398:Signal Transduction
D016356:Gene Products, tax; D020672:I-kappa B Proteins; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase