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 ch loramphenicol acetyl transferase under the control of either the full- length LTR of HTLV-I or three copies of tile tax-responsive 21-bp repe ats. We observed that treatment with okadaic acid, which inhibits the serine/threonine protein phosphatases type 1 and 2A, reduced HTLV-I LT R transcriptional activation in MT2 and K562 cells; on the contrary, t he enhancer activity of the 21-bp sequences was significantly increase d 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 inhi bitor, reduced Tax-mediated activation of both plasmids. These finding s indicated that specific serine/threonine phosphorylation events are required for Tax-mediated HTLV-I LTR activation and also suggested tha t phosphorylation at tyrosine residues is involved in this process. (C ) 1994 Academic Press, Inc.