The pleiotropic protein kinase CK2 phosphorylates HTLV-1 Tax protein in vitro, targeting its PDZ-binding motif.
The HTLV-1 transactivator Tax is an oncoprotein capable of deregulating the expression of many cellular genes and interfering with signalling pathways. Here we show that Tax-1 is phosphorylated in vitro by the pleiotropic human serine/threonine kinase CK2 at three residues, Ser-336, Ser-344 and Thr-351, close to and within its C-terminal PDZ-binding motif. We also show that the mutation of Thr-351 to aspartate abolishes Tax-1 binding to the scaffold protein hDlg, a tumour suppressor factor, while having no effect on transactivation. These results suggest that CK2, whose constitutive activity is often hijacked by viruses to sustain their vital cycle, could modulate Tax-1 oncogenic interactions.
Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Strada Le Grazie 8, Verona, Italy. carlo.bidoia@ucd.ie
Carlo
C
Bidoia
Marco
M
Mazzorana
Mario A
MA
Pagano
Giorgio
G
Arrigoni
Flavio
F
Meggio
Lorenzo A
LA
Pinna
Umberto
U
Bertazzoni
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001665:Binding Sites; D047390:Casein Kinase II / Q000378:metabolism*; D000074288:Discs Large Homolog 1 Protein; D016356:Gene Products, tax / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010766:Phosphorylation; D011485:Protein Binding; D016415:Sequence Alignment
D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D016356:Gene Products, tax; D008565:Membrane Proteins; C514970:tax protein, Human T-lymphotrophic virus 1; D047390:Casein Kinase II