Differential effects of diverse p53 isoforms on TAp73 transcriptional activity and apoptosis

The p53 activities are due, at least in part, to its ability to form oligomers that bind to specific DNA sequences and activate transcription. Since some mutant p53 proteins and Np73 isoforms form heterocomplexes with TAp73, we asked whether p53 isoforms can do the same and potentially act as dominant-negative inhibitors of TAp73. Moreover, it has already been found that some isoforms form complex with wtp53 and some of them inhibit p53 tumor-suppressor functions. Therefore, we studied the complex formation and co-immunoprecipitation assays show that all six p53 isoforms examined can form complexes with TAp73, whereas only 133p53// isoforms form complex with TAp73. All p53 isoforms counteract TAp73 transactivation function but with different efficiency and in a promoter-dependent manner. Furthermore, apoptotic activity of TAp73 was augmented by coexpression of p53, whereas 133p53 and inhibit its apoptotic activity most efficiently. We have determined the half-life of different p53 isoforms: p53 isoform has the shortest half-life, whereas 133p53 has the longest half-life. Inhibitory interactions of two proteins in complex often lead to their stabilization. However, only three isoforms (133p53, 133p53 and 40p53) stabilize TAp73. We are convinced that defining the interactions between p53/p73 would give a new insight into how the p53 isoforms modulate the p73 functions in tumorigenesis.