Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 79
Mitochondria role in the control of the activity of p53 and Rb
Ioana Pârvu-Ferecatu, Nelly Godefroy, Vincent Rincheval, Nathalie Leleu, Bernard
Mignotte and Jean-Luc Vayssière
Laboratoire de Génétique et Biologie Cellulaire (FRE CNRS 2445), Université de
Versailles Saint-Quentin-en-Yvelines et Laboratoire de Génétique Moléculaire et
Physiologique,
Ecole Pratique des Hautes Etudes, 45 avenue des Etats-Unis 78035 Versailles Cedex
We previously showed in rat embryo fibroblasts that the p53 protein can activate two distinct
two apoptotic pathways (1, 2 and 3). The first one involves p53’s targets gene transactivation,
whose products trigger a mitochondrial apoptosis that is sensitive to Bcl-2 inhibition. The
second pathway is mediated by the p53’s transcriptional repression activity, initiating a
caspase-independent and Bcl-2-insensitive massive cell death. We also reported that the Rb
tumour suppressor protein contributes to the outcome of p53 activation. Indeed, we observed
that the full length form of Rb, named p110Rb, supports the transrepressional activity of p53,
whereas its cleaved p76Rb form, generated by caspase-9, allows cell survival (3).
Here, we describe a new role for mitochondria in regulating the activity of both the p53 and
Rb proteins. Indeed, in most of the cell types we tested, the inactive p53 protein displays a
mitochondrial location under normal conditions (i.e. proliferating cells), suggesting that the
docking of p53 to mitochondria contributes to its inactivation. After stress, posttranslational
modifications (e.g.: phosphorylation) of p53 promotes its translocation towards the nucleus,
followed by either apoptosis or growth arrest. Equally, we showed for the first time a
mitochondrial location of the Rb protein which would be correlated to its ability to antagonize
p53-induced apoptosis. Thereby, these data support a model in which mitochondria play a
regulatory role of the activity of both p53 and Rb by trapping these proteins, to prevent at
least their nuclear activity.
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