MDM2

MDM2 grips the amino terminus of p53 and escorts it to the proteasome, preventing unnecessary cell-cycle arrest or apoptosis. Its RING domain partners with MDMX to transfer ubiquitin. The ligase responds to signals from ribosomal stress, DNA damage, and phosphorylation events that change its partners. p53 itself turns on MDM2 transcription, forming a feedback loop that controls response timing. Small molecules, peptides, and degrader binders that occupy the p53 pocket on MDM2 keep the tumor suppressor active. These binders also let researchers probe MDM2's other clients and map how knocking it down reshapes stress signaling in cancer cells.