%0 Journal Article %T pRb/E2F-1-mediated caspase-dependent induction of Noxa amplifies the apoptotic effects of the Bcl-2/Bcl-xL inhibitor ABT-737 %+ Centre de Recherche en Cancérologie Nantes-Angers (CRCNA) %A Bertin-Ciftci, Joséphine %A Barré, B %A Le Pen, J %A Maillet, Laurent, A %A Couriaud, C %A Juin, Philippe %A Braun, Frédéric %< avec comité de lecture %@ 1350-9047 %J Cell Death and Differentiation %I Nature Publishing Group %V 20 %N 5 %P 755 - 764 %8 2013 %D 2013 %R 10.1038/cdd.2013.6 %M 23429261 %Z Life Sciences [q-bio] %Z Life Sciences [q-bio]/CancerJournal articles %X Although Bcl-2 family members control caspase activity by regulating mitochondrial permeability, caspases can, in turn, amplify the apoptotic process upstream of mitochondria by ill-characterized mechanisms. We herein show that treatment with a potent inhibitor of Bcl-2 and Bcl-xL, ABT-737, triggers caspase-dependent induction of the BH3-only protein, Mcl-1 inhibitor, Noxa. RNA interference experiments reveal that induction of Noxa, and subsequent cell death, rely not only on the transcription factor E2F-1 but also on its regulator pRb. In response to ABT-737, pRb is cleaved by caspases into a p68Rb form that still interacts with E2F-1. Moreover, pRb occupies the noxa promoter together with E2F-1, in a caspase-dependent manner upon ABT-737 treatment. Thus, caspases contribute to trigger the mitochondrial apoptotic pathway by coupling Bcl-2/Bcl-xL inhibition to that of Mcl-1, via the pRb/E2F-1-dependent induction of Noxa. %G English %L inserm-02447042 %U https://inserm.hal.science/inserm-02447042 %~ INSERM %~ CNRS %~ UNAM %~ CRCNA