PPM1D and neoplasm: Moreover, PPM1D deactivates p38 mitogen-activated protein kinase (p38 MAPK) and downregulates the expression of its downstream effectors p16Ink4a and p19ARF, which are vital tumor suppressors and important regulators of p53 activity.32,51,68 PPM1D ultimately inhibits DNA repair, cell cycle checkpoints, and cellular apoptosis, thereby promoting proliferation and passage of corrupted genome.