YAP enhances the pro-proliferative transcriptional activity of mutant p53 proteins

Silvia Di Agostino, Giovanni Sorrentino, Eleonora Ingallina, Fabio Valenti, Maria Ferraiuolo, Silvio Bicciato, Silvano Piazza, Sabrina Strano, Giannino Del Sal, Giovanni Blandino

Research output: Contribution to journalArticlepeer-review

Abstract

Mutant p53 proteins are present in more than half of human cancers. Yes-associated protein (YAP) is a key transcriptional regulator controlling organ growth, tissue homeostasis, and cancer. Here, we report that these two determinants of human malignancy share common transcriptional signatures. YAP physically interacts with mutant p53 proteins in breast cancer cells and potentiates their pro-proliferative transcriptional activity. We found YAP as well as mutant p53 and the transcription factor NF-Y onto the regulatory regions of cyclin A, cyclin B, and CDK1 genes. Either mutant p53 or YAP depletion down-regulates cyclin A, cyclin B, and CDK1 gene expression and markedly slows the growth of diverse breast cancer cell lines. Pharmacologically induced cytoplasmic re-localization of YAP reduces the expression levels of cyclin A, cyclin B, and CDK1 genes both in vitro and in vivo. Interestingly, primary breast cancers carrying p53 mutations and displaying high YAP activity exhibit higher expression levels of cyclin A, cyclin B, and CDK1 genes when compared to wt-p53 tumors.

Original languageEnglish
Pages (from-to)188-201
Number of pages14
JournalEMBO Reports
Volume17
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

Keywords

  • gene expression
  • metabolism
  • mutant p53 and YAP
  • proliferation
  • statin

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry

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