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.
Field of science
- /natural sciences/biological sciences/zoology/mammalogy
- /social sciences/sociology/social problems/migration
- /medical and health sciences/clinical medicine/oncology/cancer
- /natural sciences/biological sciences/genetics and heredity/genome
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