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Reports
A Cytoplasmic PML Mutant Inhibits p53 Function
Cristian Bellodi, Karin Kindle, Francesca Bernassola, Andrea Cossarizza, David Dinsdale, Gerry Melino, David Heery and Paolo Salomoni
volume 5 | issue 22
15 november 2006Pages: 2688 - 2692
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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.
Authors
Cristian Bellodi
MRC Toxicology Unit, Leicester, United Kingdom
Karin Kindle
University of Nottingham, Nottingham, UK
Francesca Bernassola
University of Rome, Rome, Italy
Andrea Cossarizza
University of Modena and Reggio Emilia, Modena, Italy
David Dinsdale
MRC Toxicology Unit, Leicester, United Kingdom
Gerry Melino
University of Rome
David Heery
University of Nottingham, Nottingham, UK
Paolo Salomoni
MRC Toxicology Unit, Leicester, United Kingdom
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.