title: Phosphoproteomics reveals resveratrol-dependent inhibition of Akt/mTORC1/S6K1 signaling.
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.
authors.affiliation: Department of Biology, Stern College for Women of Yeshiva University , New York, New York 10016, United States.
authors.forename: Anya
authors.initials: A
authors.lastname: Alayev
authors.forename: Peter F
authors.initials: PF
authors.lastname: Doubleday
authors.forename: Sara Malka
authors.initials: SM
authors.lastname: Berger
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Ballif
authors.forename: Marina K
authors.initials: MK
authors.lastname: Holz
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D002853:Chromatography, Liquid; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D061986:MCF-7 Cells; D000076222:Mechanistic Target of Rapamycin Complex 1; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010748:Phosphopeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000077185:Resveratrol; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016895:Culture Media, Serum-Free; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D010748:Phosphopeptides; D010750:Phosphoproteins; D020543:Proteome; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D013267:Stilbenes; D058570:TOR Serine-Threonine Kinases; C494918:AKT1 protein, human; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1
keywords: PRAS40; S6K1; SILAC; mTORC1; phosphoproteomics; resveratrol