Phosphoproteomics Reveals
Resveratrol-Dependent Inhibition
of Akt/mTORC1/S6K1 Signaling
- Publication date
- Publisher
Abstract
Resveratrol, a plant-derived
polyphenol, regulates many cellular
processes, including cell proliferation, aging and autophagy. However,
the molecular mechanisms of resveratrol action in cells are not completely
understood. Intriguingly, resveratrol treatment of cells growing in
nutrient-rich conditions induces autophagy, while acute resveratrol
treatment of cells in a serum-deprived state inhibits autophagy. In
this study, we performed a phosphoproteomic analysis after applying
resveratrol to serum-starved cells with the goal of identifying the
acute signaling events initiated by resveratrol in a serum-deprived
state. We determined that resveratrol in serum-starved conditions
reduces the phosphorylation of several proteins belonging to the mTORC1
signaling pathway, most significantly, PRAS40 at T246 and S183. Under
these same conditions, we also found that resveratrol altered the
phosphorylation of several proteins involved in various biological
processes, most notably transcriptional modulators, represented by
p53, FOXA1, and AATF. Together these data provide a more comprehensive
view of both the spectrum of phosphoproteins upon which resveratrol
acts as well as the potential mechanisms by which it inhibits autophagy
in serum-deprived cells