P53-dependent hypusination of eIF5A affects mitochondrial translation and senescence immune surveillance.

ABSTRACT: Cellular senescence is characterized by a permanent growth arrest and is associated with tissue aging and cancer. Senescent cells secrete a number of different cytokines referred to as the senescence-associated secretory phenotype (SASP), which impacts the surrounding tissue and immune response. Here, we find that senescent cells exhibit higher rates of protein synthesis compared to proliferating cells and identify eIF5A as a crucial regulator of this process. Polyamine metabolism and hypusination of eIF5A play a pivotal role in sustaining elevated levels of protein synthesis in senescent cells. Mechanistically, we identify a p53-dependent program in senescent cells that maintains hypusination levels of eIF5A. Finally, we demonstrate that functional eIF5A is required for synthesizing mitoc

SUBMITTER: Jiang X 

PROVIDER: S-EPMC11358140 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature