c-sis/PDGF-B promoter transactivation by the Yax protein of human T-cell leukemia virus type 1.
The human c-sis proto-oncogene promoter is transactivated by the human T-cell leukemia virus type 1 Tax protein in human Jurkat T-cells. Transactivation was >7-fold in Jurkat cells stably expressing the Tax protein (Jurkat-Tax) than in Jurkat E6.1 cells and was further enhanced in Jurkat-Tax cells stimulated with 12-O-tetradecanoylphorbol-13-acetate and the calcium ionophore, ionomycin. Deletion analysis showed that a 167-base pair promoter fragment retained full Tax responsiveness. Insertion of this minimal Tax-responsive region into a heterologous, minimal promoter resulted in approximately a 7-fold increase of transcriptional activation in the presence of Tax. Linker-scanning insertion analysis of this region identified Tax-responsive elements at nucleotides -64 to -45 (TRE1) and -34 to -15 (TATA box region). TRE1 contains a consensus binding site for the Sp family of transcription factors. The TATA box region corresponds to the TATA box and its 3'-neighboring sequence. Gel-shift and antibody supershift analysis of TRE1-binding proteins in unstimulated Jurkat E6.1 and Jurkat-Tax nuclear extracts identified Sp1 and Sp3 as the main TRE1 binding factors. Nuclear extracts from stimulated Jurkat E6.1 and Jurkat-Tax cells identified an additional TRE1 binding factor, Egr-1. These studies define a novel mechanism whereby Tax transactivates the c-sis promoter.
Trejo
S R
SR
Division of Molecular Oncology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Fahl
W E
WE
Ratner
L
L
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D003001:Cloning, Molecular; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D016356:Gene Products, tax / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008156:Luciferases / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D011519:Proto-Oncogenes; D011994:Recombinant Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D013601:T-Lymphocytes; D016385:TATA Box; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016356:Gene Products, tax; C000715470:MAS1 protein, human; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D010982:Platelet-Derived Growth Factor; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D015759:Ionomycin; D008156:Luciferases; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate