Abstract
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 (DΔNp53). Historically, DΔNp53 was the first p53 isoform identified and was thought to be responsible for all p53 biological activities. It was shown that DΔNp53 induces apoptosis by inducing the expression of IAP antagonists, such as Reaper. Here we investigated the roles of Dp53 and DΔNp53 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 DΔNp53 induced Wingless (Wg) expression and enhanced proliferation in both ‘undead cells’ and in ‘genuine’ apoptotic cells. In contrast to DΔNp53, Dp53 did not induce Wg expression in the absence of the endogenous p53 gene. Thus, we propose that DΔNp53 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.
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Acknowledgements
This work was supported by grant from the CNRS (ATIP) and Ligue contre le cancer (Comités de Savoie and Puy-de-Dôme) to BM and NIH R01GM079425 to HDR. Bench fees were funded by a Marie Curie Fellowship ERG (PERG03-GA-2008-230812) to MLDD. FN was supported by a fellowship of the Association Française contre les Myopathies. Work on p53 isoforms by PH and his team is supported by a grant form the French National Cancer Institute (INCa). This work was made possible by the DROSO-TOOLS and PLATIM facilities of the UMS3444, Biosciences, Lyon, France. We thank Virginie Marcel for critical reading of the manuscript. We also thank Carmen Garrido for technical help, and our colleagues and Bloomington centre for fly stocks and reagents.
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Dichtel-Danjoy, ML., Ma, D., Dourlen, P. et al. Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation. Cell Death Differ 20, 108–116 (2013). https://doi.org/10.1038/cdd.2012.100
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DOI: https://doi.org/10.1038/cdd.2012.100
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