Generation of ?TAp73 Proteins by Translation from a Putative Internal Ribosome Entry Site
p73 belongs to a family of transcription factors, including p53 and p63, that mediate response to DNA damage and cellular stress by inducing DNA repair, cell cycle arrest, and apoptosis. TP73 gene contains two promotors and several splice variants resulting in up to 24 possible permutations of p73 proteins which underlies the complexity of the family and its regulatory mechanisms. p73 variants lacking the N-terminal, denoted as ?TAp73, are not transcriptionally competent and they act in a dominant negative fashion over TAp73. ?TAp73 isoforms can be generated by alternative promotor usage, giving rise to ?Np73, or alternative splicing of exons 2, 3 or 2, and 3 together. Such transcript isoforms potentially produce oncogenic proteins and they were shown to be present in primary tumors and tumor-derived cell lines. We investigated the possibility of additional mechanisms by which p73 protein could be regulated and discovered a putative internal ribosome entry site (IRES) in exon 2. Translation initiation of TAp73 mRNA results in a ?Np73-like peptide, thus demonstrating an additional mechanism whereby a ?TA p73 protein is produced from a transcript originally generated from the P1 promotor of the p73 gene
p73 ires p53 internal ribosome entry site