The Codon 47 Polymorphism in p53 Is Functionally Significant

摘要: In addition to a common polymorphism at codon 72, the p53 tumor suppressor gene also contains rare single nucleotide amino acid 47. Wild type encodes proline this residue, but in <5% of African Americans, is serine. Notably, phosphorylation adjacent serine 46 by proline-directed kinase p38 MAPK known greatly enhance ability induce apoptosis. Here we showed that 47 polymorphic variant, which replaces residue necessary for recognition kinases, markedly poorer substrate on MAPK. Consistent with finding, variant has up 5-fold decreased apoptosis compared wild p53. Mechanistically, found transactivate two target genes, p53AIP1 and PUMA, not other response genes; first time been implicated transactivation PUMA Down-regulation cells using short interfering RNAs reduced these level comparable containing variant. The combined data indicated that, like 72 polymorphism, functionally significant may play role cancer risk, progression, efficacy therapy.