Most human tumors contain inactivated p53 protein, either by mutations and/or functional deactivation. Restoration of wild-type p53 function could be one of the key tools in new anticancer therapy. Using an electromobility shift assay, we investigated the effect of temperature on DNA binding of wild-type and mutant p53 proteins. We showed that analysis of the DNA-binding capacity of mutant p53 proteins is complicated by the temperature at which the assay is performed. Furthermore, neither ability to bind to DNA nor conformational analysis accurately defines the transcriptional activity of human tumor-derived p53 mutant proteins. That some mutants can bind DNA and adopt a wild-type conformation in vitro, but are transcriptionally inactive in vivo, points to the involvement of cellular factors required for transactivation. Therefore, the common use of purified proteins and in vitro determinations of DNA binding and conformation are not the best indicators of the functional properties of mutant p53.

Institute of Biophysics Academy of Sciences of the Czech Republic Brno Czech Republic

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