MDMX (MDM4), a Promising Target for p53 Reactivation Therapy and Beyond

The MDMX protein was identified as a p53-interacting protein with a strong similarity to MDM2. Like Mdm2, Mdmx expression is essential for curbing p53 activity during embryonic development, indicating nonredundant functions of Mdmx and Mdm2. There is now a large body of evidence indicating that cancers frequently up-regulate MDMX expression as a means to dampen p53 tumor-suppressor function. Importantly, MDMX also shows p53-independent oncogenic functions. These data make MDMX an attractive therapeutic target for cancer therapy. Here, we summarize the mechanisms used by cancer cells to increase MDMX expression and promising pharmacological strategies to target MDMX in cancer-in particular, the recent findings that antisense oligonucleotides (ASOs) can be used to efficiently modulate MDMX messenger RNA (mRNA) splicing.