Mouse double minute 4 protein (MDM4 (also known as MDMX))

Mouse double minute 4 protein (MDM4, also known as Proto-oncogene protein mdmx) is a key negative regulator of the tumor suppressor p53. It shares structural similarity with its paralog Mouse double minute 2 (MDM2) but lacks intrinsic E3 ubiquitin ligase activity. Instead, it binds directly to p53, inhibiting its transcriptional activity under normal conditions. In response to DNA damage or genotoxic stress, post-translational modifications such as phosphorylation alter its function—allowing it together with MDM2—to promote stabilization and activation rather than degradation/inhibition of p53. Overexpression or amplification contributes significantly to oncogenesis by disabling one major cellular defense against malignant transformation.

Other names

Proto-oncogene protein mdmxMDMXDouble minute 4 proteinp53-binding protein Mdm4Mdm2-like p53-binding protein

Drugs targeting this molecule aim to inhibit the interaction between MDMX (and/or MDM2) with p53, thereby restoring or enhancing wild-type p53 function leading to cell cycle arrest or apoptosis in cancer cells with functional TP53.