Institut Jacques Monod Seminar – Carlos Estella
20 June 2025 - 11 h 45 min - 13 h 00 min
Invited by the Konstantinides Lab, Carlos Estella (Laboratory of stress response and morphogenesis. Centro de Biología Molecular CSIC-UAM, Madrid, Spain) will present an Institut Jacques Monod seminar on the theme:
A cross talk between p53 and the cell cycle regulates apoptotic induction and tumor formation in Drosophila
Abstract:
Cell division is essential for tissue regeneration and organismal survival. However, errors in this process can lead to uncontrolled cell proliferation and cancer. The tumor suppressor gene p53 plays a critical role in maintaining genomic integrity by coordinating cellular responses to stress, such as DNA damage. These responses include cell cycle arrest, DNA repair, senescence, or apoptosis. Importantly, how these responses are precisely coordinated to maintain tissue homeostasis remains poorly understood.
To address this challenge, simple genetic models are needed to study the precise regulation of cellular responses triggered by p53 and its role in tumorigenesis. To simplify the study of p53’s functions, we use Drosophila melanogaster, which has a single p53 homolog. Drosophila serves as a powerful genetic model due to its highly conserved pathways and sophisticated genetic tools. Notably, approximately 85% of human cancer-related genes have orthologs in flies. In this seminar I´ll discuss recent work from our laboratory that demonstrated how the cellular context and proliferative status of a cell significantly impact p53’s ability to regulate the various responses triggered by DNA damage. In addition, I´ll present the tumorigenic potential of p53 when its apoptotic role is inhibited. We find that cells with chronic p53 activity that have inhibited its apoptotic potential acquire a persistent activity of the JNK pathway, which drives them into a senescent-like status and induce the non-autonomous overgrowth of the surrounding tissue. These results lead us to propose a model in which cell cycle progression and p53 pro-apoptotic activity are molecularly connected to coordinate the appropriate response after DNA damage.