Akt Is S-Palmitoylated: A New Layer of Regulation for Akt
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.626404/full |
| _version_ | 1819049856788856832 |
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| author | Matías Blaustein Matías Blaustein Matías Blaustein Estefanía Piegari Estefanía Piegari Camila Martínez Calejman Antonella Vila Antonella Vila Antonella Vila Analía Amante Analía Amante Analía Amante María Victoria Manese Ari Zeida Laurence Abrami Mariela Veggetti Mariela Veggetti David A. Guertin David A. Guertin David A. Guertin F. Gisou van der Goot María Martha Corvi Alejandro Colman-Lerner Alejandro Colman-Lerner |
| author_facet | Matías Blaustein Matías Blaustein Matías Blaustein Estefanía Piegari Estefanía Piegari Camila Martínez Calejman Antonella Vila Antonella Vila Antonella Vila Analía Amante Analía Amante Analía Amante María Victoria Manese Ari Zeida Laurence Abrami Mariela Veggetti Mariela Veggetti David A. Guertin David A. Guertin David A. Guertin F. Gisou van der Goot María Martha Corvi Alejandro Colman-Lerner Alejandro Colman-Lerner |
| author_sort | Matías Blaustein |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T11:38:48Z |
| format | Article |
| id | doaj.art-da3d3759888f419e9a57f77628b1945d |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T11:38:48Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-da3d3759888f419e9a57f77628b1945d2022-12-21T19:05:22ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01910.3389/fcell.2021.626404626404Akt Is S-Palmitoylated: A New Layer of Regulation for AktMatías Blaustein0Matías Blaustein1Matías Blaustein2Estefanía Piegari3Estefanía Piegari4Camila Martínez Calejman5Antonella Vila6Antonella Vila7Antonella Vila8Analía Amante9Analía Amante10Analía Amante11María Victoria Manese12Ari Zeida13Laurence Abrami14Mariela Veggetti15Mariela Veggetti16David A. Guertin17David A. Guertin18David A. Guertin19F. Gisou van der Goot20María Martha Corvi21Alejandro Colman-Lerner22Alejandro Colman-Lerner23Departamento de Fisiología, Biología Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires, ArgentinaInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA, Buenos Aires, ArgentinaInstituto de Biociencias, Biotecnología y Biología Traslacional (iB3), Universidad de Buenos Aires, Buenos Aires, ArgentinaDepartamento de Fisiología, Biología Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires, ArgentinaInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA, Buenos Aires, ArgentinaProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United StatesDepartamento de Fisiología, Biología Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires, ArgentinaInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA, Buenos Aires, ArgentinaInstituto de Biociencias, Biotecnología y Biología Traslacional (iB3), Universidad de Buenos Aires, Buenos Aires, ArgentinaDepartamento de Fisiología, Biología Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires, ArgentinaInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA, Buenos Aires, ArgentinaInstituto de Biociencias, Biotecnología y Biología Traslacional (iB3), Universidad de Buenos Aires, Buenos Aires, ArgentinaLaboratorio de bioquímica y biología celular de parásitos, Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) – CONICET, Chascomús, ArgentinaDepartamento de Bioquímica and Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, UruguayGlobal Health Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandDepartamento de Fisiología, Biología Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires, ArgentinaInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA, Buenos Aires, ArgentinaProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United StatesDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, United StatesLei Weibo Institute for Rare Diseases, University of Massachusetts Medical School, Worcester, MA, United StatesGlobal Health Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandLaboratorio de bioquímica y biología celular de parásitos, Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) – CONICET, Chascomús, ArgentinaDepartamento de Fisiología, Biología Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires, ArgentinaInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA, Buenos Aires, ArgentinaThe 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.626404/fullAktS-palmitoylationcell signalingsubcellular localizationGolgilysosomes |
| spellingShingle | Matías Blaustein Matías Blaustein Matías Blaustein Estefanía Piegari Estefanía Piegari Camila Martínez Calejman Antonella Vila Antonella Vila Antonella Vila Analía Amante Analía Amante Analía Amante María Victoria Manese Ari Zeida Laurence Abrami Mariela Veggetti Mariela Veggetti David A. Guertin David A. Guertin David A. Guertin F. Gisou van der Goot María Martha Corvi Alejandro Colman-Lerner Alejandro Colman-Lerner Akt Is S-Palmitoylated: A New Layer of Regulation for Akt Frontiers in Cell and Developmental Biology Akt S-palmitoylation cell signaling subcellular localization Golgi lysosomes |
| title | Akt Is S-Palmitoylated: A New Layer of Regulation for Akt |
| title_full | Akt Is S-Palmitoylated: A New Layer of Regulation for Akt |
| title_fullStr | Akt Is S-Palmitoylated: A New Layer of Regulation for Akt |
| title_full_unstemmed | Akt Is S-Palmitoylated: A New Layer of Regulation for Akt |
| title_short | Akt Is S-Palmitoylated: A New Layer of Regulation for Akt |
| title_sort | akt is s palmitoylated a new layer of regulation for akt |
| topic | Akt S-palmitoylation cell signaling subcellular localization Golgi lysosomes |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.626404/full |
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