Program in Molecular Medicine; Department of Molecular, Cell and Cancer Biology; Lei Weibo Institute for Rare Diseases
Amino Acids, Peptides, and Proteins | Cell Biology | Enzymes and Coenzymes | Molecular Biology
The protein kinase Akt/PKB participates in a great variety of processes, including translation, cell proliferation and survival, as well as malignant transformation and viral infection. In the last few years, novel Akt posttranslational modifications have been found. However, how these modification patterns affect Akt subcellular localization, target specificity and, in general, function is not thoroughly understood. Here, we postulate and experimentally demonstrate by acyl-biotin exchange (ABE) assay and (3)H-palmitate metabolic labeling that Akt is S-palmitoylated, a modification related to protein sorting throughout subcellular membranes. Mutating cysteine 344 into serine blocked Akt S-palmitoylation and diminished its phosphorylation at two key sites, T308 and T450. Particularly, we show that palmitoylation-deficient Akt increases its recruitment to cytoplasmic structures that colocalize with lysosomes, a process stimulated during autophagy. 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. These results 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.
Akt, Golgi, S-palmitoylation, autophagy, cell differentiation, cell signaling, lysosomes, subcellular localization
Rights and Permissions
Copyright © 2021 Blaustein, Piegari, Martínez Calejman, Vila, Amante, Manese, Zeida, Abrami, Veggetti, Guertin, van der Goot, Corvi and Colman-Lerner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI of Published Version
Blaustein M, Piegari E, Martínez 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. Akt Is S-Palmitoylated: A New Layer of Regulation for Akt. Front Cell Dev Biol. 2021 Feb 15;9:626404. doi: 10.3389/fcell.2021.626404. PMID: 33659252; PMCID: PMC7917195. Link to article on publisher's site
Frontiers in cell and developmental biology
Blaustein M, Piegari E, Calejman CM, Vila A, Amante A, Manese MV, Zeida A, Abrami L, Veggetti M, Guertin DA, van der Goot FG, Corvi MM, Colman-Lerner A. (2021). Akt Is S-Palmitoylated: A New Layer of Regulation for Akt. Open Access Publications by UMMS Authors. https://doi.org/10.3389/fcell.2021.626404. Retrieved from https://escholarship.umassmed.edu/oapubs/4598
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.