Affordable Access

Access to the full text

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

Authors
  • Blaustein, Matías1, 2, 3
  • Piegari, Estefanía1, 2
  • Martínez Calejman, Camila4
  • Vila, Antonella1, 2, 3
  • Amante, Analía1, 2, 3
  • Manese, María Victoria5
  • Zeida, Ari6
  • Abrami, Laurence7
  • Veggetti, Mariela1, 2
  • Guertin, David A.4, 8, 9
  • van der Goot, F. Gisou7
  • Corvi, María Martha5
  • Colman-Lerner, Alejandro1, 2
  • 1 Departamento de Fisiología, Biología Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires , (Argentina)
  • 2 Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA, Buenos Aires , (Argentina)
  • 3 Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3), Universidad de Buenos Aires, Buenos Aires , (Argentina)
  • 4 Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA , (United States)
  • 5 Laboratorio de bioquímica y biología celular de parásitos, Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) – CONICET, Chascomús , (Argentina)
  • 6 Departamento de Bioquímica and Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo , (Uruguay)
  • 7 Global Health Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne , (Switzerland)
  • 8 Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA , (United States)
  • 9 Lei Weibo Institute for Rare Diseases, University of Massachusetts Medical School, Worcester, MA , (United States)
Type
Published Article
Journal
Frontiers in Cell and Developmental Biology
Publisher
Frontiers Media SA
Publication Date
Feb 15, 2021
Volume
9
Identifiers
DOI: 10.3389/fcell.2021.626404
Source
Frontiers
Keywords
Disciplines
  • Cell and Developmental Biology
  • Original Research
License
Green

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 3H-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.

Report this publication

Statistics

Seen <100 times