Clarifying functions of the p53 protein is a crucial aspect of cancer research. We analyzed the binding sites of p53 wild-type (WT) protein and its oncologically significant mutants and evaluated their transactivation properties using a functional yeast assay. Unlike the binding sites as determined in myeloid leukemia cell lines by chromatin immunoprecipitation of p53-R175H, p53-Y220C, p53-M237I, p53-R248Q, and p53-R273H mutants, the target sites of p53-WT and p53-R282W were significantly associated with putative G-quadruplex sequences (PQSs). Guanine-quadruplex (G-quadruplex or G4) formation in these sequences was evaluated by using a set of biophysical methods. G4s can modulate gene expression induced by p53. At low p53 expression level, PQS upstream of the p53-response element (RE) leads to greater gene expression induced by p53-R282W compared to that for the RE without PQS. Meanwhile, p53-WT protein expression is decreased by the PQS presence. At a high p53 expression level, the presence of PQS leads to a decreased expression of the reporter regardless of the distance and localization of the G4 from the RE.

BioTechMed Graz Mozartgasse 12 2 Graz A 8010 Austria

Department of Food Chemistry and Biotechnology Faculty of Chemistry Brno University of Technology Purkyňova 118 Brno 612 00 Czech Republic

Institute of Biophysics of the Czech Academy of Sciences Královopolská 135 Brno 612 65 Czech Republic

Laboratory of Computer Aided Molecular Design Division of Medicinal Chemistry Otto Loewi Research Center Neue Stiftingtalstr 6 3 Graz A 8010 Austria

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