CDK4 Phosphorylates AMPKα2 to Inhibit Its Activity and Repress Fatty Acid Oxidation.

Détails

ID Serval
serval:BIB_F02666506F7E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
CDK4 Phosphorylates AMPKα2 to Inhibit Its Activity and Repress Fatty Acid Oxidation.
Périodique
Molecular Cell
Auteur(s)
Lopez-Mejia I.C., Lagarrigue S., Giralt A., Martinez-Carreres L., Zanou N., Denechaud P.D., Castillo-Armengol J., Chavey C., Orpinell M., Delacuisine B., Nasrallah A., Collodet C., Zhang L., Viollet B., Hardie D.G., Fajas L.
ISSN
1097-4164 (Electronic)
ISSN-L
1097-2765
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
68
Numéro
2
Pages
336-349.e6
Langue
anglais
Résumé
The roles of CDK4 in the cell cycle have been extensively studied, but less is known about the mechanisms underlying the metabolic regulation by CDK4. Here, we report that CDK4 promotes anaerobic glycolysis and represses fatty acid oxidation in mouse embryonic fibroblasts (MEFs) by targeting the AMP-activated protein kinase (AMPK). We also show that fatty acid oxidation (FAO) is specifically induced by AMPK complexes containing the α2 subunit. Moreover, we report that CDK4 represses FAO through direct phosphorylation and inhibition of AMPKα2. The expression of non-phosphorylatable AMPKα2 mutants, or the use of a CDK4 inhibitor, increased FAO rates in MEFs and myotubes. In addition, Cdk4(-/-) mice have increased oxidative metabolism and exercise capacity. Inhibition of CDK4 mimicked these alterations in normal mice, but not when skeletal muscle was AMPK deficient. This novel mechanism explains how CDK4 promotes anabolism by blocking catabolic processes (FAO) that are activated by AMPK.

Mots-clé
AMP-Activated Protein Kinases/genetics, AMP-Activated Protein Kinases/metabolism, Animals, Cyclin-Dependent Kinase 4/genetics, Cyclin-Dependent Kinase 4/metabolism, Embryo, Mammalian/metabolism, Fatty Acids/genetics, Fatty Acids/metabolism, Fibroblasts/metabolism, Mice, Mice, Knockout, Muscle, Skeletal/metabolism, Mutation, Oxidation-Reduction, Physical Conditioning, Animal, AMPK, CDK4, FAO, metabolism, mitochondria
Pubmed
Web of science
Création de la notice
09/11/2017 21:41
Dernière modification de la notice
20/08/2019 17:18
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