Impairment of p53 acetylation, stability and function by an oncogenic transcription factor

Alessandra Insinga, Silvia Monestiroli, Simona Ronzoni, Roberta Carbone, Mark Pearson, Giancarlo Pruneri, Giuseppe Viale, Ettore Appella, PierGiuseppe Pelicci, Saverio Minucci

Research output: Contribution to journalArticlepeer-review


Mutations of p53 are remarkably rare in acute promyelocytic leukemias (APLs). Here, we demonstrate that the APL-associated fusion proteins PML-RAR and PLZF-RAR directly inhibit p53, allowing leukemic blasts to evade p53-dependent cancer surveillance pathways. PML-RAR causes deacetylation and degradation of p53, resulting in repression of p53 transcriptional activity, and protection from p53-dependent responses to genotoxic stress. These phenomena are dependent on the expression of wild-type PML, acting as a bridge between p53 and PML-RAR. Recruitment of histone deacetylase (HDAC) to p53 and inhibition of p53 activity were abrogated by conditions that either inactivate HDACs or trigger HDAC release from the fusion protein, implicating recruitment of HDAC by PML-RAR as the mechanism underlying p53 inhibition.

Original languageEnglish
Pages (from-to)1144-1154
Number of pages11
JournalEMBO Journal
Issue number5
Publication statusPublished - Mar 10 2004


  • Histone deacetylase
  • P53
  • PML
  • Promyelocytic leukemia

ASJC Scopus subject areas

  • Cell Biology
  • Genetics


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