1. HTLV-1 Tax protein recruitment into IKKε and TBK1 kinase complexes enhances IFN-I expression
- Author
-
Maria Grazia Romanelli, Umberto Bertazzoni, Erica Diani, Elisa Bergamo, Giorgia Cremonese, and Francesca Avesani
- Subjects
Transcriptional Activation ,TRAF3 ,IKKε ,Cell signaling ,TBK1 ,Tax ,Tax proteins ,Protein Serine-Threonine Kinases ,Biology ,IFN ,IFN beta ,IB kinase (IKK) ,Transactivation ,TANK-binding kinase 1 ,HTLV ,Virology ,Humans ,Promoter Regions, Genetic ,Human T-lymphotropic virus 1 ,TNF Receptor-Associated Factor 3 ,Kinase ,Gene Products, tax ,Interferon-beta ,IRF3 ,HTLV-I Infections ,I-kappa B Kinase ,Cancer research ,Phosphorylation ,Protein Binding ,Interferon regulatory factors - Abstract
The Tax protein expressed by human T-cell leukemia virus type 1 (HTLV-1) plays a pivotal role in the deregulation of cellular pathways involved in the immune response, inflammation, cell survival, and cancer. Many of these effects derive from Tax multiple interactions with host factors, including the subunits of the IKK-complex that are required for NF-κB activation. IKKɛ and TBK1 are two IKK-related kinases that allow the phosphorylation of interferon regulatory factors that trigger IFN type I gene expression. We observed that IKKɛ and TBK1 recruit Tax into cellular immunocomplexes. We also found that TRAF3, which regulates cell receptor signaling effectors, forms complexes with Tax. Transactivation analyses revealed that expression of Tax, in presence of IKKɛ and TBK1, enhances IFN-β promoter activity, whereas the activation of NF-κB promoter is not modified. We propose that Tax may be recruited into the TBK1/IKKɛ complexes as a scaffolding-adaptor protein that enhances IFN-I gene expression.
- Published
- 2015