Human T cell leukemia virus type 1 tax protein increases NF-kappa B dimer formation and antagonizes the inhibitory activity of the I kappa B alpha regulatory protein.
Human T cell leukemia virus type 1 (HTLV-1) encodes a strong transcriptional transactivator, the Tax protein, that stimulates viral transcription through the long terminal repeat and also stimulates many cellular genes via the activation of host transcription factors. Previous studies have demonstrated that Tax activates NF-kappa B through binding to the Rel homology domain of NF-kappa B proteins. Tax was also shown to increase degradation of I kappa B alpha resulting in the induction of NF-kappa B DNA binding activity. We addressed the specificity and function of Tax interaction with members of the NF-kappa B/I kappa B alpha family by using EMSA, protein affinity chromatography, protein-protein crosslinking and co-immunoprecipitation assays. The results of the present study demonstrate that: (1) Tax enhances NF-kappa B binding to DNA 40- to 100-fold by increasing NF-kappa B dimer formation which can be detected in the absence of DNA; (2) Tax binds to all NF-kappa B DNA binding subunits in vitro and to I kappa B alpha; (3) Tax physically associates with I kappa B alpha in vivo; and (4) Tax and I kappa B alpha have antagonistic effects on NF-kappa B binding and gene activity. These results suggest that Tax interaction with I kappa B alpha interferes with the formation of NF-kappa B-I kappa B alpha complexes and may play a role in targeting I kappa B alpha for degradation.
Petropoulos
L
L
Lady Davis Institute for Medical Research, McGill University, Montreal, Canada.
Lin
R
R
Hiscott
J
J
D001667:Binding, Competitive; D002154:Calpain / Q000037:antagonists & inhibitors; D002460:Cell Line; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D007096:Imidoesters; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020569:Proto-Oncogene Proteins c-rel; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D016356:Gene Products, tax; D007096:Imidoesters; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; C497593:RELB protein, human; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051841:Transcription Factor RelB; C029326:dimethyl pimelimidate; D004247:DNA; D002154:Calpain