Role of the p53 pathway in metabolism: implications in normal development, aging and cancer

Summary: Mutation of the TP53 gene is the most frequent genetic alteration in human cancers. Tumor suppressive functions of p53 have been linked to its ability to control cell division, cell death and cellular senescence. However growing evidence indicates that the metabolic functions of p53 play important roles in cancer progression. Our team has been studying the metabolic functions of the p53 pathway for many years and highlighted previously unknown functions of several key components of this molecular cascade in pyruvate, amino-acid, and nucleotide metabolism. Beyond cancer development, I will illustrate how deregulation of these metabolic networks impacts on normal physiological responses in the liver, contributes to cancer development and leads to inborn metabolic disorders.

Relevant publications:

1-  Riscal R. et al (2016) Chromatin-bound MDM2 regulates serine metabolism and redox homeostasis independently of p53. Mol. Cell. Jun 16;62(6):890-902.

2-    Arena et al. Mitochondrial MDM2 regulates respiratory complex I activity independently of p53. Mol Cell 2018

3-  Cissé et al. Targeting MDM2-dependent serine metabolism as a new therapeutic strategy for liposarcoma. Sci Trans Med 2020

4-    Lacroix et al. The multifunctional protein E4F1 links p53 to lipid metabolism in adipocytes. Nat Comms 2021

5-    Di Michele et al. E4F1 coordinates pyruvate metabolism and the activity of the Elongator Complex to ensure protein translation fidelity. BioRxiv

Biography: Laurent LE CAM is the head of the « Molecular Oncogenesis » laboratory and deputy director at the Institut de Recherche en Cancérologie de Montpellier (INSERM U1194). He graduated from Montpellier University in 1999 and then moved to Pr P. Sicinski’s laboratory at the Dana Faber Cancer Institute (Boston, USA) where he developed several genetically engineered mouse models to evaluate the in vivo functions of cell cycle regulators. After his recruitment at INSERM in 2003, he started to study the role of different regulators of the p53 pathway, with a particular interest in understanding their role in metabolism. His team develops multidisciplinary research projects standing at the frontier of different fields including cancer development, inborn metabolic disorders and normal physiological responses to nutrient challenges.