Tax-induced HTLV-I LTR transcriptional activation is modulated by phosphorylation.
We studied the effect of protein phosphatase and kinase inhibitors on Tax-mediated transcription of constructs carrying the reporter gene chloramphenicol acetyl transferase under the control of either the full-length LTR of HTLV-I or three copies of the tax-responsive 21-bp repeats. We observed that treatment with okadaic acid, which inhibits the serine/threonine protein phosphatases type 1 and 2A, reduced HTLV-I LTR transcriptional activation in MT2 and K562 cells; on the contrary, the enhancer activity of the 21-bp sequences was significantly increased in both cell lines; treatment with the protein kinase C inhibitor H-7 blocked Tax-mediated transcription of both constructs. We also found that treatment with sodium orthovanadate, a tyrosine phosphatase inhibitor, reduced Tax-mediated activation of both plasmids. These findings indicated that specific serine/threonine phosphorylation events are required for Tax-mediated HTLV-I LTR activation and also suggested that phosphorylation at tyrosine residues is involved in this process.
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Institute of Oncology, Interuniversity Center for Cancer Research (CIRC), Padova, Italy.
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Chieco-Bianchi
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D001483:Base Sequence; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D016356:Gene Products, tax; D009838:Oligodeoxyribonucleotides; D011493:Protein Kinase C; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases