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

Oncogene | Oct 26, 2000

http://www.ncbi.nlm.nih.gov/pubmed/11064457

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.

Pubmed ID: 11064457 RIS Download

Mesh terms: Binding Sites | Enzyme Activation | Gene Products, tax | Human T-lymphotropic virus 1 | I-kappa B Kinase | I-kappa B Proteins | Protein Binding | Protein Subunits | Protein-Serine-Threonine Kinases | Recombinant Fusion Proteins | Signal Transduction