P53ADHESION · The role of the Drosophila tumor suppressor gene p53 in apoptosis and adhesion
FP7 — People (Marie Curie Actions)
- Duration
- 2008-10-01 → 2011-09-30
- EU contribution
- €45,000
- Participants
- 1
- Scheme
- MC-ERG
Lines connect the coordinator with its partners.
Results in brief
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.
Data: CORDIS, © European Union
Project objective
Apoptosis is a form of cell death ubiquitously used in animals, which participates in development and in the adult in defense against potentially dangerous cells. Not surprisingly, deregulation of cell death has severe consequences for the developing organism and adult. Inappropriate cell death is associated with many disorders including degenerative neurological diseases (excess of cell death) and cancer (loss of cell death). One of the important components of the cell death machinery is the p53 transcription factor. p53 is often described as the 'guardian of the genome' because it is a critical component of the cellular mechanisms that respond to genotoxic stresses like DNA damage and hypoxia to maintain the genomic integrity in part by arresting cell-cycle progression or by inducing apoptosis. In Drosophila, p53 is also involved in genome integrity maintenance and also in development. In mammals, emerging evidence shows that the contribution of the tumour suppressor p53 to the control of tumorigenesis is not restricted to its well-known anti-proliferative activities, but is extended to other stages of cancer development, i.e. the modulation of cell migration. In drosophila, several evidences are suggesting that p53 could also have additional roles and also participate in cell adhesion and/or polarity maintenance control. Our goal is to extend the investigation on p53 function in drosophila during development. We propose to follow two recent results that have been proposed in mammals: first to understand the function of p53 in the control of cell adhesion and also to study the alternative splicing of p53 in drosophila taking into consideration the recent discovery of two p53-related genes, p63 and p73 and their different isoforms. Finally we would like to address if and how the expression of p53 is triggered when the development of a normal epithelium is impaired.
Original text from CORDIS.
Participants
- ECOLE NORMALE SUPERIEURE DE LYON · LYONCoordinatorFrance
Links
Data: CORDIS, © European Union