JNK targets p53 ubiquitination and degradation in nonstressed cells

Abstract

In this study we elucidated the role of nonactive JNK in regulating p53 stability. The amount of p53–JNK complex was inversely correlated with p53 level. A peptide corresponding to the JNK binding site on p53 efficiently blocked ubiquitination of p53. Similarly, p53 lacking the JNK binding site exhibits a longer half-life than p53^wt. Outcompeting JNK association with p53 increased the level of p53, whereas overexpression of a phosphorylation mutant form of JNK inhibited p53 accumulation. JNK–p53 and Mdm2–p53 complexes were preferentially found in G₀/G₁and S/G₂M phases of the cell cycle, respectively. Altogether, these data indicate that JNK is an Mdm2-independent regulator of p53 stability in nonstressed cells.