Akt Is S-Palmitoylated: A New Layer of Regulation for Akt

BLAUSTEIN, M; PIEGARI, E; MARTINEZ CALEJMAN, C; VILA, A; AMANTE, A; MANESE, MV; ZEIDA, A; ABRAMI, L; VEGGETTI, M; GUERTIN, DA; VAN DER GOOT, FG; CORVI, MM; COLMAN-LERNER, A

Front. Cell Dev. Biol.

Frontiers Editorial Office

Lugar: Laussane; Año: 2021 vol. 9

The protein kinase Akt/PKB participates in a great variety of processes, includingtranslation, cell proliferation and survival, as well as malignant transformation and viralinfection. In the last few years, novel Akt posttranslational modifications have beenfound. However, how these modification patterns affect Akt subcellular localization,target specificity and, in general, function is not thoroughly understood. Here, wepostulate and experimentally demonstrate by acyl-biotin exchange (ABE) assay and 3Hpalmitate metabolic labeling that Akt is S-palmitoylated, a modification related to proteinsorting throughout subcellular membranes. Mutating cysteine 344 into serine blockedAkt S-palmitoylation and diminished its phosphorylation at two key sites, T308 andT450. Particularly, we show that palmitoylation-deficient Akt increases its recruitmentto cytoplasmic structures that colocalize with lysosomes, a process stimulated duringautophagy. Finally, we found that cysteine 344 in Akt1 is important for proper its function,since Akt1-C344S was unable to support adipocyte cell differentiation in vitro. Theseresults add an unexpected new layer to the already complex Akt molecular code,improving our understanding of cell decision-making mechanisms such as cell survival,differentiation and death.