Figure 3.

SIRT7 promotes p53 stabilization in response to distinct stressors. In response to UV-induced stress, SIRT7 is activated by ATR-mediated phosphorylation. Activated SIRT7 efficiently deacetylates its nucleolar target nucleophosmin (NPM), facilitating its exclusion from nucleoli. Deacetylated NPM binds and inhibits the ubiquitin ligase MDM2, thereby preventing MDM2- dependent ubiquitination and subsequent proteasomal degradation of p53 (left panel). In response to glucose starvation, SIRT7 translocates from the nucleolus, associates and deacetylates PCAF, which favors PCAF-mediated degradation of MDM2, leading to p53 stabilization (right panel).