The rare nonsense mutation in p53 triggers alternative splicing to produce a protein capable of inducing apoptosis

• DOI: 10.1371/journal.pone.0185126
• Publication Date: 2017-09-29T13:37:49Z
• Authors: Evgeny M. Makarov; Tatyana A. Shtam; Roman A. Kovalev; Rimma A. Pantina; Elena Yu Varfolom...; Michael V. Filatov
• Keywords: Nonsense mutation; Mutant protein

P53 protein is more frequently mutated in human tumours compared with the other proteins. While majority of p53 mutations, especially within its DNA-binding domain, lead to loss wild-type function, there are accumulating data demonstrating that mutants gain tumour promoting activities; latter triggers a revitalised interest functional analysis mutants. A systematic screening for mutations surgical materials from patients glioma revealed 378C>G mutation creates stop codon at position amino acid residue 126. The eliminates recognition site restriction endonuclease Sca I allowed us carry out RFLP DNA extracted clinical samples and suggests this frequent than documented databases. Both ECV-304 EJ cell lines, probably originate bladder carcinoma T24 line, were confirmed contain homozygous but shown produce expected full-length size detected by Western blotting. We provide evidence generates an alternative 3' splice (ss) which often used instead authentic upstream ss, driving production mRNA encoding single deletion (p53ΔY126). Using endogenous expression, we demonstrated p53ΔY126 nearly as active wild type inducing p21/Waf1 expression apoptosis.