UMMS Affiliation

Program in Molecular Medicine; Department of Molecular, Cell and Cancer Biology; Lei Weibo Institute for Rare Diseases

Publication Date

2021-02-15

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cell Biology | Enzymes and Coenzymes | Molecular Biology

Abstract

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.

Keywords

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

10.3389/fcell.2021.626404

Source

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

Journal/Book/Conference Title

Frontiers in cell and developmental biology

Related Resources

Link to Article in PubMed

PubMed ID

33659252

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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