Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Mouse double minute 4 (MDM4), also known as MDMX or HDMX (human MDMX), is a critical negative regulator of the tumor suppressor p53. Under normal growth conditions, MDM4 contributes to the repression of p53 activity. Upon DNA damage, it becomes important to down-regulate MDM4 to allow a full p53 response. Here, the mechanisms by which MDM4 activity is controlled are reviewed and discussed, starting with alterations in copy number, then control of transcription, mRNA stability, translation, and finally post-translational interactions, modifications, localization, and targeting by recently developed drugs.