TY - JOUR
T1 - Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation
AU - Dichtel-Danjoy, M.-L.
AU - Ma, D.
AU - Dourlen, P.
AU - Chatelain, G.
AU - Napoletano, F.
AU - Robin, M.
AU - Corbet, M.
AU - Levet, C.
AU - Hafsi, H.
AU - Hainaut, P.
AU - Ryoo, H.D.
AU - Bourdon, J.-C.
AU - Mollereau, B.
N1 - Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013
Y1 - 2013
N2 - 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 (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 IAP antagonists, such as Reaper. Here we investigated the roles of Dp53 and D?Np53 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 D?Np53 induced Wingless (Wg) expression and enhanced proliferation in both 'undead cells' and in 'genuine' apoptotic cells. In contrast to D?Np53, Dp53 did not induce Wg 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.
AB - 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 (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 IAP antagonists, such as Reaper. Here we investigated the roles of Dp53 and D?Np53 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 D?Np53 induced Wingless (Wg) expression and enhanced proliferation in both 'undead cells' and in 'genuine' apoptotic cells. In contrast to D?Np53, Dp53 did not induce Wg 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.
UR - http://www.scopus.com/inward/record.url?scp=84870990619&partnerID=8YFLogxK
U2 - 10.1038/cdd.2012.100
DO - 10.1038/cdd.2012.100
M3 - Article
C2 - 22898807
AN - SCOPUS:84870990619
SN - 1350-9047
VL - 20
SP - 108
EP - 116
JO - Cell Death & Differentiation
JF - Cell Death & Differentiation
IS - 1
ER -