Figure 1.

Mechanisms of SIRT7-dependent p53 stabilization in response to stress. A. Ultraviolet (UV) irradiation increases the catalytic activity of sirtuin 7 (SIRT7) by promoting SIRT7 phosphorylation by Ataxia telangiectasia mutated and Rad3 related kinase (ATR). Activated SIRT7 deacetylates nucleophosmin (NPM), which leaves nucleoli and binds to the ubiquitin ligase murine double minute 2 (MDM2), thereby inhibiting MDM2-dependent p53 ubiquitination and degradation. B. Glucose starvation facilitates release of SIRT7 from nucleoli, allowing interaction with the acetyltransferase p300/CBP-associated factor (PCAF). SIRT7 deacetylates PCAF, which subsequently binds to MDM2, thus promoting MDM2 ubiquitination and destabilization, resulting in accumulation of p53. C. SIRT7 inhibits p53 accumulation following exposure to high doses of doxorubicin, in neurons exposed to ischemia/reperfusion injury and in cardiomyocytes following hypoxia/reoxygenation-induced stress