Association between HTLV-1 Tax and I kappa B alpha is dependent on the I kappa B alpha phosphorylation state.
Biological, molecular, and epidemiological data have demonstrated that human T cell leukemia virus type 1 (HTLV-1) encoded Tax protein plays a central role in the initiation of T cell malignancy. The 40-kDa Tax oncoprotein serves as a potent transcriptional activator that induces viral gene expression driven by the HTLV-1 long ... terminal repeats and also stimulates multiple cellular genes involved in T cell activation, cell cycle regulation, and gene activation. Since Tax has been shown to interact directly and indirectly with the NF-kappa B/I kappa B regulatory proteins, we examined the significance of an in vivo association between Tax and the I kappa B alpha inhibitor. Using GST affinity chromatography, Tax was shown to interact with the I kappa B alpha ankyrin repeats which are essential for interaction with the NF-kappa B/Rel proteins. In vivo, using I kappa B alpha mutants and co-immunoprecipitation, a preferential interaction between HTLV-1 Tax and N-terminally hypophosphorylated I kappa B alpha was detected. Tax also enhanced binding of I kappa B alpha to the proteasome subunit HsN3, resulting in a Tax-enhanced, constitutive degradation of wild-type and mutated forms of I kappa B alpha in the absence of phosphorylation and ubiquitination. Binding of I kappa B alpha to proteasome subunit HC9 was also observed, but this interaction occurred independently of Tax. Taken together, these results suggest a role for Tax as a viral chaperone resulting in the enhanced constitutive turnover of I kappa B alpha. The association of Tax with hypophosphorylated I kappa B alpha may prevent I kappa B alpha from binding to NF-kappa B and also target I kappa B alpha to the proteasome for degradation via a phosphorylation-independent pathway.
Mesh Terms:
3T3 Cells, Animals, Ankyrins, Binding Sites, Cell Line, Cysteine Endopeptidases, DNA-Binding Proteins, Gene Expression Regulation, Viral, Gene Products, tax, Human T-lymphotropic virus 1, Humans, I-kappa B Proteins, Mice, Multienzyme Complexes, NF-kappa B, Phosphorylation, Proteasome Endopeptidase Complex, Protein Binding, Protein Conformation, Structure-Activity Relationship, Transcriptional Activation
3T3 Cells, Animals, Ankyrins, Binding Sites, Cell Line, Cysteine Endopeptidases, DNA-Binding Proteins, Gene Expression Regulation, Viral, Gene Products, tax, Human T-lymphotropic virus 1, Humans, I-kappa B Proteins, Mice, Multienzyme Complexes, NF-kappa B, Phosphorylation, Proteasome Endopeptidase Complex, Protein Binding, Protein Conformation, Structure-Activity Relationship, Transcriptional Activation
Virology
Date: Dec. 05, 1998
PubMed ID: 9875328
View in: Pubmed Google Scholar
Download Curated Data For This Publication
121208
Switch View:
- Interactions 2