Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation. Bertrand Mollereau¹, Marie-Laure Dichtel-Danjoy¹, Dali Ma¹, Pierre Dourlen¹, Gilles Chatelain¹, Francesco Napoletano¹, Marion Robin¹, Marlene Corbet¹, Clemence Levet¹, Hind Hafsi², Pierre Hainaut², Hyung Don Ryoo³, Jean Christophe Bourdon⁴. 1) LBMC UMR5239, Ecole Normale Superieure, Lyon, France; 2) International Agency for Research on Cancer, Lyon, France; 3) Department of Cell Biology, New York University School of Medicine, New York, NY, USA; 4) European Associated Laboratory University of Dundee/Inserm U858, Department of surgery and Molecular Oncology, Dundee, DD1 9SY UK.

   Epithelial tissues have the intrinsic capability to repair and regenerate following irradiation or genetically induced cell death. However, how epithelial cells respond to injury and recover is not well understood. In the past few years, studies from metazoan models such as Drosophila forged the concept of apoptosis-induced proliferation, a process by which damaged cells entering apoptosis signal the surrounding unaffected cells to divide so to recoup the tissue loss. Importantly, the findings made in Drosophila have greatly impacted the understanding of tumor repopulation during cancer irradiation and also the process of regeneration in vertebrates. In Drosophila, apoptotic cells play an active role in proliferation, where the caspase Dronc (caspase 9 homolog) 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 (DNp53). Historically, DNp53 was the first p53 isoform identified and was thought to be responsible for all p53 biological activities. Here, we investigated the roles of Dp53 and DNp53 in apoptosis and 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. The ability of apoptotic cells to secrete mitogenic signals may be of major significance in regeneration processes and in the development of tumors.