Unveiling the Developmental and Tumor Suppressive Roles of the p53 variant, p53psi

However, heterozygote mating fails to yield viable p53psi homozygote knock-in (p53KI/KI) pups, indicating that forced p53psi expression disrupts embryogenesis. Timed mating studies revealed that homozygous p53psi expression is embryonically lethal at day E16.5. Embryos at E14.5-16.5 were pale, reduced in size, and exhibited exencephaly, a defect typically associated with a failure in neural tube closure.

Mouse embryonic fibroblasts (MEFs) derived from p53psi embryos and transformed with the E1A and H-RasV12 oncogenes formed tumors with a decreased growth rate compared to their p53null counterparts, suggesting that p53psi retains at least some tumor-suppressive functions. Our mechanistic studies suggest that p53psi modulates tumorigenesis by triggering senescence. These findings provide new insights into the role of the p53psi variant, paving the way for a better interpretation of TP53 mutational patterns in human cancers.