Association of HTLV Tax proteins with TAK1-binding protein 2 and RelA in calreticulin-containing cytoplasmic structures participates in Tax-mediated NF-κB activation.
HTLV-1 is more pathogenic than HTLV-2 despite having a similar genome and closely related transactivating oncoproteins. Both Tax-1 protein from HTLV-1 and Tax-2 from HTLV-2 activate the NF-κB pathway. The mechanisms involved in Tax-1 deregulation of this signalling pathway have been thoroughly investigated, but little is known about regulation by Tax-2. We have compared the interaction of Tax-1 and Tax-2 with two key NF-κB signalling factors: TAK1-binding protein 2 (TAB2), an adaptor involved in the activation of TAK1 kinase, and RelA, the active subunit of the canonical RelA/p50 NF-κB transcription factor. Tax-2 formed stable complexes with both RelA and TAB2. These two NF-κB factors colocalized with Tax proteins in dotted cytoplasmic structures targeted by calreticulin, a multi-process calcium-buffering chaperone. Co-expression of RelA and/or TAB2 markedly increased Tax-mediated NF-κB activation. These findings provide new insights into the role of RelA, TAB2 and Tax in the deregulation of the NF-κB pathway.
Avesani
Francesca
F
Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Strada Le Grazie 8, Verona, Italy. francesca.avesani_01@univr.it
Romanelli
Maria Grazia
MG
Turci
Marco
M
Di Gennaro
Gianfranco
G
Sampaio
Carla
C
Bidoia
Carlo
C
Bertazzoni
Umberto
U
Bex
Françoise
F
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D037282:Calreticulin / Q000032:analysis*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D022083:Cytoplasmic Structures / Q000737:chemistry / Q000821:virology*; D016356:Gene Products, tax / Q000276:immunology / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D015367:Human T-lymphotropic virus 2 / Q000276:immunology; D006801:Humans; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D051996:Transcription Factor RelA / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D037282:Calreticulin; D016356:Gene Products, tax; D016328:NF-kappa B; C498143:RELA protein, human; C410585:TAB2 protein, human; D051996:Transcription Factor RelA; C514970:tax protein, Human T-lymphotrophic virus 1; C514971:tax protein, Human T-lymphotrophic virus 2