Guinea pig p53 mRNA: Identification of new elements in coding and untranslated regions and their functional and evolutionary implications

We report the sequence of the guinea pig p53 cDNA. The comparative analysis of the coding and noncoding regions of p53 cDNAs of all available complete vertebrate sequences has allowed us to single out new conserved signals po ssibly involved in p53 functional activity. We have focused our attention o n the most variable region of the protein, the proline (P)-rich domain, sug gested to play a fundamental role in antiproliferative pathways. In this do main we have identified the PXXXXP repeated motif and singled out a common consensus sequence that can be considered a signature for mammalian p53: PX XXXPX{0,4}PX{0,9}PA-(T,P,I,)(S,P)WPL. We have demonstrated the significance of the PXXXXP motif in SH3-binding protein and suggested its structure to be a loop. Also, the 5' and 3' untranslated regions (UTRs) of the guinea pi g were sequenced, and this study represents the first detailed structural a nalysis of the UTRs of the p53 mRNAs available in literature. The 5' UTR of guinea pig (233 nt) can be folded into a stable secondary structure resemb ling that predicted in mouse. The 3' UTR of guinea pig is 771 nt long and s hows higher similarity with human than with rodent sequences, having a regi on of about 350 nt that is deleted in rat and mouse. In the 3' UTR we have identified the presence of a mammalian-wide interspersed repeat sequence an d of a cytoplasmic polyadenylation element, which could be involved in tran slational activation by promoting polyadenylation of mRNA, providing inform ation about a possible mechanism of regulation of p53 expression mediated b y the 3' UTR of the mRNA. The observations presented here could open new av enues to targeted mutations and experimental approaches useful in investiga ting new regulation mechanisms of p53 translation, activity, and stability. (C) 1999 Academic Press.