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.
Cardellino
Umberto
U
Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d'Aosta, Genoa, Italy.
Ciribilli
Yari
Y
Andreotti
Virginia
V
Modesto
Paola
P
Menichini
Paola
P
Fronza
Gilberto
G
Pellegrino
Claudio
C
Inga
Alberto
A
D000818:Animals; D002371:Cat Diseases / Q000235:genetics*; D002415:Cats; D019143:Evolution, Molecular; D015870:Gene Expression; D006801:Humans; D008957:Models, Genetic; D016296:Mutagenesis; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D020218:Response Elements; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D016159:Tumor Suppressor Protein p53