Sp1 is a key regulator of the PDGF beta-receptor transcription.
The mouse PDGF beta-receptor promoter is tightly controlled by NF-Y that binds to a CCAAT box located upstream of the initiation site [1, 2]. In this report, we show that Sp1 plays an essential role in the PDGF beta-receptor transcription. Within the upstream GC rich area there are two Sp1 binding sites located in close proximity to the CCAAT box. Deletion of the GC rich region resulted in a 50% decrease of the transcriptional activity of the promoter, and a complete loss of its responsiveness to over-expression of Sp1. There was an additive effect between NF-Y and Sp I in reporter activity when they were co-transfected together with the promoter-reporter construct. Furthermore, transfection of NF-Y failed to enhance transcriptional activity when the Sp1 binding sites were deleted from the promoter, suggesting an important role for Sp1 in this NF-Y controlled transcription. We have recently reported that c-Myc represses PDGF beta-receptor transcription through its interference with the transactivation activity of NF-Y [3]. In the case of p21(wafl/cip1) transcription, c-Myc was shown to repress its transcription by sequestering Sp1 [4]. However, we could not find any effect of Sp1 in the c-Myc-mediated repression on the PFDGF beta-receptor promoter, since the deletion of SpI binding sites could not attenuate the repression by c-Myc on the promoter activity.
Molander
C
C
Institute of Anatomy and Cell Biology, Göteborg University, Gothenburg, Sweden.
Hackzell
A
A
Ohta
M
M
Izumi
H
H
Funa
K
K
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D023081:CCAAT-Binding Factor; D009838:Oligodeoxyribonucleotides; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D004247:DNA; D020797:Receptor, Platelet-Derived Growth Factor beta