Pharmacological activation of p53 induces dose-dependent changes in endothelial cell fate during angiogenic sprouting.

ABSTRACT: The cell cycle is a key regulator of endothelial cell specification into tip and stalk cell phenotypes, which are essential for angiogenesis in both normal development and pathological conditions. While the tumor suppressor p53 is known to regulate the cell cycle and influence cell fate, its role in modulating the cell fate of these phenotypes remains unclear. Using non-genotoxic small molecule and stapled peptide compounds to pharmacologically activate p53 via MDM2 inhibition, we demonstrate that graded levels of p53 induce distinct cellular fates in normal endothelial cells. Low levels of p53 induce reversible cell cycle arrest by reducing DNA replication, while high levels induce senescence and cell death. Surprisingly, all tested levels of p53 activation reduced the growth of venous bl

SUBMITTER: Al-Radi O 

PROVIDER: S-EPMC12698774 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature