P53 tumour suppressor modulates transcription of the TATA-less gene coding for the tumour-associated carbonic anhydrase MN/CA IX in MaTu cells.
MN/CA IX (MN) exhibits a strong association with tumours. Co-transfection experiments revealed that in MaTu cells the activity of the (-173;+31) MN promoter construct was repressed by the wild type p53 in a dose-responsive manner and stimulated by the (143(Val-->Ala)) mutant. Upregulation of endogenous p53 by mitomycin C treatment in MaTu cells also had a profound effect on MN expression as well as the activity of MN promoter in a reporter construct. p53 can thus modulate MN expression and at least in a subset of tumours the changed p53 status might be responsible for MN positivity. Co-transfections with internally deleted MN promoter constructs demonstrated that the wild type p53 exerts its repression activity on the level of the basal transcriptional machinery and not on a particular cis element within the MN promoter.
Kaluzová
M
M
Institute of Virology, Slovak Academy of Sciences, Dúbravská cesta 9, 842 45, Bratislava, Slovak Republic.
Pastoreková
S
S
Pastorek
J
J
Kaluz
S
S
D002256:Carbonic Anhydrases / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D016158:Genes, p53; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D002256:Carbonic Anhydrases