Akt is S-palmitoylated: a new layer of regulation for Akt

ALEJANDRO COLMAN-LERNER; MATIAS BLAUSTEIN; ESTEFANIA PIEGARI; MARTINEZ CALEJMAN, CAMILA

Frontiers in Cell and Developmental Biology

Frontiers Editorial Office

Año: 2021

The protein kinase Akt/PKB participates in a great variety of processes, including translation, cell proliferation and survival aswell as malignant transformation and viral infection. In the last few years, novel Akt posttranslational modifications have beenfound. However, how these modification patterns affect Akt subcellular localization, target specificity and function is notthoroughly understood. Here, we postulate and experimentally demonstrate by acyl-biotin exchange (ABE) assay and 3H-palmitatelabeling that Akt is S-palmitoylated, a modification related to protein sorting throughout subcellular membranes. Mutating cysteine344 into serine blocked Akt S-palmitoylation and diminished its phosphorylation at two key sites, T308 and T450. Particularly, weshow that palmitoylation-deficient Akt increases its recruitment to cytoplasmic structures that colocalize with lysosomes, aprocess stimulated during autophagy. Finally, we found that Akt1 cysteine 344 is important for proper Akt function, sinceAkt1-C344S was unable to support adipocyte cell differentiation in vitro. These results add an unexpected new layer to the alreadycomplex Akt molecular code, improving our understanding of cell decision-making mechanisms such as cell survival, differentiationand death.