p53-binding domain found in MDM4 and similar proteins
MDM4, also known as double minute 4 protein, MDM2-like p53-binding protein, protein MDMX, HDMX, or p53-binding protein MDM4, exerts its oncogenic activity predominantly by binding the p53 tumor suppressor and blocking its transcriptional activity. MDM4 is phosphorylated and destabilized in response to DNA damage stress. It can also be specifically dephosphorylated through directly interacting with protein phosphatase 1 (PP1), which may increase its stability and thus inhibit p53 activity. MDM4 also has a p53-independent role in tumorigenesis and cell growth regulation. MDM4 contains an N-terminal p53-binding domain and a C-terminal zinc RING-finger domain responsible for its hetero-oligomerization, which is crucial for the suppression of P53 activity during embryonic development and the recruitment of E2 ubiquitin-conjugating enzymes. MDM4 also harbors a RanBP2-type zinc finger (zf-RanBP2) domain near the central acidic region.
Jiyao W et al.(2023). "The conserved domain database in 2023.",