Key promoter elements involved in transcriptional activation of the cancer-related gene coding for S100P calcium-binding protein.
S100P gene encodes a calcium-binding protein expressed in different tumor tissues and is functionally implicated in malignant phenotype. Despite consistent relationship to cancer, regulation of S100P gene expression has remained unexplored. Here we determined the transcription start and defined the S100P core promoter. Using a series of the promoter constructs analyzed by dual luciferase reporter assay, we identified SMAD, STAT/CREB and SP/KLF binding sites as critical cis-elements required for S100P expression in cancer cells. We also demonstrated in EMSA that these elements bind nuclear factors, and showed their functional significance by promoter deletion analysis. This study represents the first coherent contribution to understanding of factors and pathways responsible for S100P gene activation in cancer.
Gibadulinova
Adriana
A
Centre of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia.
Oveckova
Ingrid
I
Parkkila
Seppo
S
Pastorekova
Silvia
S
Pastorek
Jaromir
J
D001483:Base Sequence; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020218:Response Elements / Q000235:genetics*; D050791:STAT Transcription Factors / Q000378:metabolism; D017384:Sequence Deletion; D051785:Smad Proteins / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
C115163:CREB1 protein, human; D002135:Calcium-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; C103003:S100P protein, human; D050791:STAT Transcription Factors; D051785:Smad Proteins; D016329:Sp1 Transcription Factor; C080774:erythroid Kruppel-like factor; D008156:Luciferases