Malbert-Colas, Ponnuswamy and colleagues found that MDMX (also known as MDM4) binds to nascent TP53 mRNA on phosphorylation of MDMX by the DNA damage response kinase ataxia-telangiectasia mutated (ATM). This binding allows the correct folding of the internal ribosome entry sequence (IRES) in TP53 mRNA, which in turn allows MDM2 binding and promotes TP53 translation. MDM2 can prevent MDMX binding to TP53 mRNA, whereas ATM-phosphorylated MDM2 promoted MDMX binding to TP53 mRNA. Therefore, MDM2 and MDMX have non-redundant but synergistic effects on TP53 mRNA translation that may be important in cancer.