Regulation of p53-mediated p53 degradation. (A) The binding of Mdm2 to p53 promotes the ubiquitination of p53 and its subsequent degradation by the proteasome. (B) DNA damage induces covalent modifications of p53 and Mdm2, particularly phosphorylation (indicated by (P)). Phosphorylation within the Mdm2-p53 binding interface can block binding and thereby protect p53 from degradation. (C) Phosphorylation of Mdm2 within domain(s) required for its biochemical activity will also block p53 degradation, even if Mdm2-p53 binding is maintained. (D) Deregulated oncoproteins induce the synthesis of ARF, which binds to Mdm2 and prevents its action. Abbreviations: Ub, ubiquitin monomer. N and C denote the amino and carboxyl terminus, respectively, of each protein.
From: Oren, M. (1999) Regulation of the p53 Tumor Suppressor Protein. J. Biol. Chem. 274, 36031-36034 (html) (pdf)