Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation.
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.
Group Apoptosis and Neurogenetics, Laboratory of Molecular Biology of the Cell, CNRS UMR5239, Ecole Normale Supérieure de Lyon, UMS3444 Biosciences Lyon Gerland, Université de Lyon, Lyon, France.
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Dichtel-Danjoy
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Ma
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Dourlen
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Chatelain
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Napoletano
M
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Robin
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M
Corbet
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C
Levet
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Hafsi
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Hainaut
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Ryoo
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Bourdon
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Mollereau
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53