Gain of function of mutant p53: The mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation

Silvia Di Agostino, Sabrina Strano, Velia Emiliozzi, Valentina Zerbini, Marcella Mottolese, Ada Sacchi, Giovanni Blandino, Giulia Piaggio

Research output: Contribution to journalArticlepeer-review

Abstract

This article investigates the mechanistic aspects of mutant p53 "gain of function" in response to DNA damage. We show that mutant forms of p53 protein interact with NF-Y. The expression of cyclin A, cyclin B1, cdk1, and cdc25C, as well as the cdk1-associated kinase activities, is upregulated after DNA damage, provoking a mutant p53/NF-Y-dependent increase in DNA synthesis. Mutant p53 binds NF-Y target promoters and, upon DNA damage, recruits p300, leading to histone acetylation. The recruitment of mutant p53 to the CCAAT sites is severely impaired upon abrogation of NF-YA expression. Endogenous NF-Y, mutant p53, and p300 proteins form a triple complex upon DNA damage. We demonstrate that aberrant transcriptional regulation underlies the ability of mutant p53 proteins to act as oncogenic factors.

Original languageEnglish
Pages (from-to)191-202
Number of pages12
JournalCancer Cell
Volume10
Issue number3
DOIs
Publication statusPublished - Sep 2006

Keywords

  • CELLCYCLE
  • DNA

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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