Sp1 is involved in a protein kinase C-independent activation of human T cell leukemia virus type I long terminal repeat by 12-O-tetradecanoylphorbol-13-acetate.
The long terminal repeat (LTR) of human T cell leukemia virus type-I (HTLV-I) contains binding sites for several cellular transcription factors that can activate its expression independently of the viral transactivator Tax protein. In a previous study, we have shown that 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a Tax-independent activation of the viral LTR expression. We have also noted that although most other TPA biological effects are attributed to its protein kinase C (PKC)-activating potential, this particular effect of TPA is PKC independent and antagonized by PKC activity. In addition, we have demonstrated that deletion of the ets-responsive region 1 (ERR-1) from the LTR abolishes its response to TPA. In the present study, we demonstrate that TPA exerts this effect by enhancing the binding of the Sp1 transcription factor to an Sp1-binding site located within ERR-1. This Sp1-binding stimulation was not diminished by a potent PKC-specific inhibitor like bisindolylmaleimide-I, indicating that it did not depend on PKC activity. However, no increase in Sp1 protein level could be detected in the TPA-treated cells, suggesting that TPA exerted its effect by a posttranslational modification of Sp1 protein rather than by stimulating its synthesis. Although the proximal Tax responsive 21-bp element also contains an Sp1-binding site, the present study shows that the modified Sp1 protein mediates the TPA effect on LTR only through the Sp1 site of the ERR-1.
Torgeman
A
A
Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, 84105, Israel.
Mor-Vaknin
N
N
Aboud
M
M
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001483:Base Sequence; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016356:Gene Products, tax / Q000378:metabolism; D016325:HIV Long Terminal Repeat; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D019169:Jurkat Cells; D008301:Maleimides / Q000494:pharmacology; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D015183:Restriction Mapping; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D020079:Terminal Repeat Sequences / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation