title: HTLV-1 Tax protein recruitment into IKKε and TBK1 kinase complexes enhances IFN-I expression.
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.
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134 Verona, Italy. Electronic address: erica.diani@univr.it.
authors.forename: Erica
authors.initials: E
authors.lastname: Diani
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134 Verona, Italy. Electronic address: francesca.avesani@gmail.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: Avesani
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134 Verona, Italy. Electronic address: elisa.bergamo@univr.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bergamo
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134 Verona, Italy. Electronic address: giorgia.cremonese@gmail.com.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Cremonese
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134 Verona, Italy. Electronic address: umberto.bertazzoni@univr.it.
authors.forename: Umberto
authors.initials: U
authors.lastname: Bertazzoni
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134 Verona, Italy. Electronic address: mariagrazia.romanelli@univr.it.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Romanelli
mesh_terms: D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D015490:HTLV-I Infections / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D048008:TNF Receptor-Associated Factor 3 / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D016356:Gene Products, tax; D048008:TNF Receptor-Associated Factor 3; C514970:tax protein, Human T-lymphotrophic virus 1; D016899:Interferon-beta; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; D051550:I-kappa B Kinase
keywords: Cell signaling; HTLV; IFN; IKKε; IRF3; TBK1; Tax