Resveratrol-induced p53 activation is associated with autophagy in mouse embryonic stem cells

Highlights: • Resveratrol-induced p53 activation does not cause G1/S cell cycle checkpoint and differentiation in mESCs. • The level of resveratrol-induced p53 activity is regulated by SIRT1 deacetylation in mESCs. • Resveratrol-activated p53 stimulates autophagy in a transcription-dependent manner in mESCs. Resveratrol is a natural polyphenol with several therapeutic effects, in particular, inducing p53-dependent cell cycle arrest and/or apoptosis in tumor cells. Resveratrol-induced p53 activation may trigger differentiation and apoptosis in embryonic stem cells (ESCs). We show that resveratrol activates p53 that is negatively regulated by SIRT1 deacetylation on Lys379 and positively by AMPK phosphorylation on Ser15 in mouse ESCs (mESCs). Surprisingly, the resveratrol-activated p53 is not associated with either G1/S cell cycle checkpoint or apoptosis in mESCs. Instead, it stimulates autophagy in a transcriptional-dependent manner involving up-regulation of dram1 gene expression. This study demonstrates a novel mechanism of resveratrol-dependent p53 activation in mESCs.