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Final Report Summary - P53ADHESION (The role of the Drosophila tumor suppressor gene p53 in apoptosis and adhesion)

Irradiated or injured cells enter apoptosis and in turn promote proliferation of surrounding unaffected cells. In Drosophila, apoptotic cells play 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 fulllength isoform (Dp53) and an N-terminally truncated isoform (D∆Np53). Historically, D∆Np53 was the first p53 isoform identified and was thought to be responsible for all p53 biological activities. It was shown that D∆Np53 induces apoptosis by inducing the expression of IAPantagonists, such as Reaper. Here, we investigated the roles of Dp53 and D∆Np53 in apoptosis and apoptosis-induced proliferation. We found that both isoforms are capable of activating apoptosis but that they each induce distinct IAP-antagonists. Expression of D∆Np53 induced Wingless expression and enhanced proliferation in both “undead cells” and in “genuine” apoptotic cells. In contrast to D∆Np53, Dp53 did not induce Wingless expression in the absence of the endogenous p53 gene. Thus we propose that D∆Np53 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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ECOLE NORMALE SUPERIEURE DE LYON
France
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