A cytoplasmic PML mutant inhibits p53 function

Cristian Bellodi, Karin Kindle, Francesca Bernassola, Andrea Cossarizza, David Dinsdale, Gerry Melino, David Heery, Paolo Salomoni

Research output: Contribution to journalArticle

Abstract

The promyelocytic leukaemia gene (Pml) is a tumor suppressor identified in acute promyelocytic leukaemia (APL), where it is fused to RARα gene as a result of the chromosomal translocation t(15;17). Pml encodes both nuclear and cytoplasmic isoforms. While nuclear PML has been intensively investigated, cytoplasmic PML proteins are less characterized. PML nuclear isoforms (nPML) are the essential components of sub-nuclear structures referred to as PML nuclear bodies (PML-NB). In response to cellular insults such as DNA damage and oncogenic activation, nPML modulates p53 activity through CBP-mediated acetylation and activates its pro-apoptotic and growth suppressive functions. Two missense mutations resulting in truncated PML cytoplasmic proteins (Mut PML) have been identified in aggressive APL cases. Here we report that cytoplasmic PML is able to induce the relocation of nPML to the cytoplasm, thus reducing the number of PML-NBs. Remarkably, Mut PML inhibits p53 transcriptional, growth suppressive, and apoptotic functions, thus suggesting that cytoplasmic expression of PML has an impact on survival through inhibition of nuclear PML. Overall our findings shed new light on the role of PML cytoplasmic proteins in the regulation of p53.

Original languageEnglish
Pages (from-to)2688-2692
Number of pages5
JournalCell Cycle
Volume5
Issue number22
Publication statusPublished - Nov 15 2006

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Keywords

  • Cell death
  • Cytoplasm
  • Leukaemia
  • p53
  • PML

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Bellodi, C., Kindle, K., Bernassola, F., Cossarizza, A., Dinsdale, D., Melino, G., Heery, D., & Salomoni, P. (2006). A cytoplasmic PML mutant inhibits p53 function. Cell Cycle, 5(22), 2688-2692.