PML is a direct p53 target that modulates p53 effector functions

Elisa De Stanchina, Emmanuelle Querido, Masako Narita, Ramana V. Davuluri, Pier Paolo Pandolfi, Gerardo Ferbeyre, Scott W. Lowe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

274 Scopus citations

Abstract

The p53 tumor suppressor promotes cell cycle arrest or apoptosis in response to stress. Previous work suggests that the promyelocytic leukemia gene (PML) can act upstream of p53 to enhance transcription of p53 targets by recruiting p53 to nuclear bodies (NBs). We show that PML is itself a p53 target gene that also acts downstream of p53 to potentiate its antiproliferative effects. Hence, p53 is required for PML induction in response to oncogenes and DNA damaging chemotherapeutics. Furthermore, the PML gene contains p53 binding sites that confer p53 responsiveness to a heterologous reporter and can bind p53 in vitro and in vivo. Finally, cells lacking PML show a reduced propensity to undergo senescence or apoptosis in response to p53 activation, despite the induction of several p53 target genes. These results identify an additional element of PML regulation and establish PML as a mediator of p53 tumor suppressor functions.

Original languageEnglish (US)
Pages (from-to)523-535
Number of pages13
JournalMolecular cell
Volume13
Issue number4
DOIs
StatePublished - Feb 27 2004

Funding

We thank K.S. Chang, K. van der Kraan, A. Levine, J.R. Nevins, F.L. Graham, D.P. Baker, S. Mayilvahanan, and T. Ley for reagents; E.R. Flores for technical advice; M.E. McCurrach for technical and editorial assistance; A.W. Lin, J.T. Zilfou, and M.T. Hemann for critical reading of the manuscript; and members of the Lowe Lab for encouragement and comments. This work was supported by a Tularik postdoctoral fellowship (E.d.S.), a fellowship from the Canadian Institutes of Health and Research (E.Q.), and by grants 86239 from the CIHR (G.F.) and AG16379 from the National Institutes of Health (S.W.L.).

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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