p53–Mdm2—the affair that never ends

The p53-Mdm2 paradigm represents the best-studied relationship between a tumor suppressor gene which functions as a transcription factor and an oncogene, which functions primarily as an E3 protein ligase. The intimate relationship between these two partners has expanded to include almost every cellular biological system - from development, to growth control and programmed cell death. The affair between Mdm2 and p53 is closely controlled by a complex array of post-translational modifications, which in turn dictates the stability and activity of p53 and Mdm2. Functional diversity depends on the association with a large subset of partner proteins, which dictates the type of activity and corresponding selectivity. Here we summarize the current understanding of post-translational modifications and their effect on conformation-based functional relationship between Mdm2 and p53, as it pertains to their diverse cellular biological functions.