Hyung Don Ryoo, Clemence Levet, Pierre Hainaut, Francesco Napoletano, Marion Robin, M. Corbet, Jean-Christophe Bourdon, Bertrand Mollereau, Dali Ma, Marie-Laure Dichtel-Danjoy, Gilles Chatelain, Hind Hafsi, Pierre Dourlen, Dichtel-Danjoy, M. -L., Ma, D., Dourlen, P., Chatelain, G., Napoletano, F., Robin, M., Corbet, M., Levet, C., Hafsi, H., Hainaut, P., Ryoo, H. D., Bourdon, J. -C., Mollereau, B., Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Molecular Carcinogenesis Group, International Agency for Cancer Research (IACR), Sect Mech Carcinogenesis, Department of Cell Biology, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Division of Medical Sciences, University of Dundee-Centre for Oncology and Molecular Medicine, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Irradiated or injured cells enter apoptosis, and in turn, promote proliferation of surrounding unaffected cells. In Drosophila, apoptotic cells have an active role in proliferation, where the caspase Dronc and p53 induce mitogen expression and growth in the surrounding tissues. The Drosophila p53 gene structure is conserved and encodes at least two protein isoforms: a full-length isoform (Dp53) and an N-terminally truncated isoform (DDNp53). Historically, DDNp53 was the first p53 isoform identified and was thought to be responsible for all p53 biological activities. It was shown that DDNp53 induces apoptosis by inducing the expression of IAP antagonists, such as Reaper. Here we investigated the roles of Dp53 and DDNp53 in apoptosis and apoptosis- induced proliferation. We found that both isoforms were capable of activating apoptosis, but that they each induced distinct IAP antagonists. Expression of DDNp53 induced Wingless (Wg) expression and enhanced proliferation in both ‘undead cells’ and in ‘genuine’ apoptotic cells. In contrast to DDNp53, Dp53 did not induce Wg expression in the absence of the endogenous p53 gene. Thus, we propose that DDNp53 is the main isoform that regulates apoptosis-induced proliferation. Understanding the roles of Drosophila p53 isoforms in apoptosis and in apoptosis-induced proliferation may shed new light on the roles of p53 isoforms in humans, with important implications in cancer biology.