Gain-of-function p53 mutants have widespread genomic locations partially overlapping with p63

Elena Martynova, Silvia Pozzi, Valentina Basile, Diletta Dolfini, Federico Zambelli, Carol Imbriano, Giulio Pavesi, Roberto Mantovani

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

p53 and p63 are transcription factors -TFs- playing master roles in the DNA-damage response and in the development and maintenance of pluristratified epithelia, respectively. p53 mutations are common in epithelial tumors and HaCaT keratinocytes harbor two p53 alleles -H179Y and R282Q- with gain-of-function (GOF) activity. Indeed, functional inactivation of mutp53 affects the growth rate of HaCaT. We investigated the strategy of mutp53, by performing ChIP-Seq experiments of mutp53 and p63 and analyzed the transcriptome after mutp53 inactivation. Mutp53 bind to 7135 locations in vivo, with a robust overlap with p63. De novo motifs discovery recovered a p53/p63RE with high information content in sites bound by p63 and mutp53/p63, but not by mutp53 alone: these sites are rather enriched in elements of other TFs. The HaCaT p63 locations are only partially overlapping with those of normal keratinocytes; importantly, and enriched in mutp53 sites which delineate a functionally different group of target genes. Our data favour a model whereby mutp53 GOF mutants act both by tethering growth-controlling TFs and highjacking p63 to new locations.

Original languageEnglish (US)
Pages (from-to)132-143
Number of pages12
JournalOncotarget
Volume3
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Keratinocytes
  • Mutant p53
  • P63

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Gain-of-function p53 mutants have widespread genomic locations partially overlapping with p63'. Together they form a unique fingerprint.

  • Cite this

    Martynova, E., Pozzi, S., Basile, V., Dolfini, D., Zambelli, F., Imbriano, C., Pavesi, G., & Mantovani, R. (2012). Gain-of-function p53 mutants have widespread genomic locations partially overlapping with p63. Oncotarget, 3(2), 132-143. https://doi.org/10.18632/oncotarget.447