Transcriptional properties of feline p53 and its tumour-associated mutants: a yeast-based approach.

Mutations at the tumour suppressor gene TP53 are associated with nearly half of human cancers, but they appear to be rare ( approximately 10%) in feline neoplasms. The reasons for this difference are presently unclear but might be related to evolutionary divergence of p53 functions. To begin exploring this issue, we developed a yeast-based functional assay to measure the transcriptional ability of wild-type (wt) or mutant feline p53 (fe_p53) in comparison with human or murine p53 (hu_p53, mo_p53). fe_p53 cDNA was cloned and expressed in a panel of yeast reporter strains engineered to contain the ADE2 or the luciferase gene under p53 control via different p53 response elements. We established that wt fe_, hu_ and mo_p53 can act as transcription factors in yeast with overlapping DNA sequence specificities. Random mutagenesis and phenotypic evaluation of fe_ and hu_p53 cDNAs was also performed, revealing equal susceptibility to deleterious mutations. Five tumour-associated fe_p53 mutants exhibited a similar impact on the transactivation capacity (partial or complete loss) compared to the corresponding hu_p53 mutants. Given the high conservation of the intrinsic functional properties of fe_p53, further studies will be needed to clarify the role of p53 in feline carcinogenetic pathways.