E3 ubiquitin-protein ligase Mdm2 (MDM2) (MDM2)

E3 ubiquitin-protein ligase Mdm2 (MDM2), frequently referred to as HDM2 in human contexts, is the primary negative regulator of the p53 tumor suppressor protein. It functions by binding to the N-terminal transactivation domain of p53, which physically blocks p53-mediated transcription and targets the protein for polyubiquitination and subsequent proteasomal degradation. In many human cancers, such as soft tissue sarcomas and certain leukemias, MDM2 is overexpressed or amplified, leading to the functional inactivation of wild-type p53 and promoting tumor growth and survival. Therapeutic strategies focus on small-molecule inhibitors that disrupt the MDM2-p53 protein-protein interaction, thereby stabilizing p53 levels and restoring its ability to induce cell cycle arrest or apoptosis. Clinical development of these inhibitors is primarily targeted at patients with TP53-wild-type tumors, though therapeutic utility has been challenged by dose-limiting hematological toxicities.

Other names

HDM2Human double minute 2Oncoprotein Mdm2Double minute 2 proteinp53-binding protein Mdm2RING-type E3 ubiquitin transferase Mdm2

Inhibition of the MDM2-p53 protein-protein interaction, leading to p53 stabilization and activation of p53-mediated tumor suppression pathways.