Oncogenic intra-p53 family member interactions in human cancers

Maria Ferraiuolo, Silvia Di Agostino, Giovanni Blandino, Sabrina Strano

Research output: Contribution to journalArticlepeer-review


The p53 gene family members p53, p73, and p63 display several isoforms derived from the presence of internal promoters and alternative splicing events. They are structural homologs but hold peculiar functional properties. p53, p73, and p63 are tumor suppressor genes that promote differentiation, senescence, and apoptosis. p53, unlike p73 and p63, is frequently mutated in cancer often displaying oncogenic "gain of function" activities correlated with the induction of proliferation, invasion, chemoresistance, and genomic instability in cancer cells. These oncogenic functions are promoted either by the aberrant transcriptional cooperation of mutant p53 (mutp53) with transcription cofactors (e.g., NF-Y, E2F1, Vitamin D Receptor, Ets-1, NF-kB and YAP) or by the interaction with the p53 family members, p73 and p63, determining their functional inactivation. The instauration of these aberrant transcriptional networks leads to increased cell growth, low activation of DNA damage response pathways (DNA damage response and DNA double-strand breaks response), enhanced invasion, and high chemoresistance to different conventional chemotherapeutic treatments. Several studies have clearly shown that different cancers harboring mutant p53 proteins exhibit a poor prognosis when compared to those carrying wild-type p53 (wt-p53) protein. The interference of mutantp53/p73 and/or mutantp53/p63 interactions, thereby restoring p53, p73, and p63 tumor suppression functions, could be among the potential therapeutic strategies for the treatment of mutant p53 human cancers.

Original languageEnglish
Article number77
JournalFrontiers in Oncology
Issue numberMAR
Publication statusPublished - 2016


  • Apoptosis
  • Differentiation
  • Gain of function
  • Homology
  • Isoforms
  • P53 gene family members
  • Protein-protein interaction
  • Target genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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