Expression of homologues for p53 and p73 in the softshell clam (Mya arenaria), a naturally-occurring model for human cancer

Homologues for human p53 (Hsp53) and p73 (Hsp73) genes were cloned and expr ession patterns for their corresponding proteins analysed in tissues from n ormal and leukemic softshell clams (Mya arenaria). These are the first stru ctural and functional data for p53 and p73 cDNAs and gene products in a nat urally occurring, nonmammalian disease model. Core sequence of the predicte d clam p53 (Map53) and p73 (Map73) proteins is virtually identical and incl udes the following a highly conserved regions: the transcriptional activati on domain (TAD), MDM2 binding site, ATM phosphorylation site, proline rich domain, DSA binding domains (DBDs) II-V, nuclear import and export signals and the tetramerization domain. The core sequence is a structural mosaic of the corresponding human proteins, with the TAD and DBDs resembling Hsp53 a nd Hsp73, respectively. This suggests that Map53 and Map73 proteins mag fun ction similarly to human proteins. Clam proteins have either a short (Map53 ) or long (Map73) C-terminal extension, These features suggest that Map53 a nd Map73 mag be alternate splice variants of a p63/p73-like ancestral gene. Map73 is significantly upregulated in hemocytes and adductor muscle from l eukemic clams. In leukemic hemocytes, both proteins are absent from the nuc leus and sequestered in the cytoplasm, This observation suggests that a non -mutational p53/p73-dependent mechanism may be in col,ed in the clam diseas e. Further studies of these gene products in clams may reveal p53/p73-relat ed molecular mechanisms that are held in common with Burkitt's lymphoma or other human cancers.