Regulatory O-GlcNAcylation sites on FoxO1 ...
Type de document :
Article dans une revue scientifique
PMID :
URL permanente :
Titre :
Regulatory O-GlcNAcylation sites on FoxO1 are yet to be identified
Auteur(s) :
Fardini, Yann [Auteur]
Perez-Cervera, Yobana [Auteur]
Camoin, Luc [Auteur]
Pagesy, Patrick [Auteur]
Lefebvre, Tony [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Issad, Tarik [Auteur]
Perez-Cervera, Yobana [Auteur]
Camoin, Luc [Auteur]
Pagesy, Patrick [Auteur]
Lefebvre, Tony [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Issad, Tarik [Auteur]
Titre de la revue :
Biochemical and biophysical research communications
Nom court de la revue :
Biochem. Biophys. Res. Commun.
Numéro :
462
Pagination :
151-158
Date de publication :
2015-06-26
ISSN :
1090-2104
Mot(s)-clé(s) en anglais :
Post-translational modification
Amino Acid Sequence
O-GlcNAc transferase
O-GlcNAc glycosylation
Humans
Molecular Sequence Data
Acetylglucosamine
Forkhead transcription factor box O
Glycosylation
Recombinant Fusion Proteins
Sequence Homology, Amino Acid
Tandem Mass Spectrometry
Animals
Site-directed mutagenesis
HEK293 Cells
Mice
Protein Processing, Post-Translational
Forkhead Box Protein O1
Binding Sites
Forkhead Transcription Factors
Transcriptional activity
Amino Acid Sequence
O-GlcNAc transferase
O-GlcNAc glycosylation
Humans
Molecular Sequence Data
Acetylglucosamine
Forkhead transcription factor box O
Glycosylation
Recombinant Fusion Proteins
Sequence Homology, Amino Acid
Tandem Mass Spectrometry
Animals
Site-directed mutagenesis
HEK293 Cells
Mice
Protein Processing, Post-Translational
Forkhead Box Protein O1
Binding Sites
Forkhead Transcription Factors
Transcriptional activity
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
O-GlcNAcylation is a reversible post-translational modification that regulates cytosolic and nuclear proteins. We and others previously demonstrated that FoxO1 is O-GlcNAcylated in different cell types, resulting in an ...
Lire la suite >O-GlcNAcylation is a reversible post-translational modification that regulates cytosolic and nuclear proteins. We and others previously demonstrated that FoxO1 is O-GlcNAcylated in different cell types, resulting in an increase in its transcriptional activity. Four O-GlcNAcylation sites were identified in human FOXO1 but directed mutagenesis of each site individually had modest (T317) or no effect (S550, T648, S654) on its O-GlcNAcylation status and transcriptional activity. Moreover, the consequences of mutating all four sites had not been investigated. In the present work, we mutated these sites in the mouse Foxo1 and found that mutation of all four sites did not decrease Foxo1 O-GlcNAcylation status and transcriptional activity, and would even tend to increase them. In an attempt to identify other O-GlcNAcylation sites, we immunoprecipitated wild-type O-GlcNAcylated Foxo1 and analysed the tryptic digest peptides by mass spectrometry using High-energy Collisional Dissociation. We identified T646 as a new O-GlcNAcylation site on Foxo1. However, site directed mutagenesis of this site individually or together with all four previously identified residues did not impair Foxo1 O-GlcNAcylation and transcriptional activity. These results suggest that residues important for the control of Foxo1 activity by O-GlcNAcylation still remain to be identified.Lire moins >
Lire la suite >O-GlcNAcylation is a reversible post-translational modification that regulates cytosolic and nuclear proteins. We and others previously demonstrated that FoxO1 is O-GlcNAcylated in different cell types, resulting in an increase in its transcriptional activity. Four O-GlcNAcylation sites were identified in human FOXO1 but directed mutagenesis of each site individually had modest (T317) or no effect (S550, T648, S654) on its O-GlcNAcylation status and transcriptional activity. Moreover, the consequences of mutating all four sites had not been investigated. In the present work, we mutated these sites in the mouse Foxo1 and found that mutation of all four sites did not decrease Foxo1 O-GlcNAcylation status and transcriptional activity, and would even tend to increase them. In an attempt to identify other O-GlcNAcylation sites, we immunoprecipitated wild-type O-GlcNAcylated Foxo1 and analysed the tryptic digest peptides by mass spectrometry using High-energy Collisional Dissociation. We identified T646 as a new O-GlcNAcylation site on Foxo1. However, site directed mutagenesis of this site individually or together with all four previously identified residues did not impair Foxo1 O-GlcNAcylation and transcriptional activity. These results suggest that residues important for the control of Foxo1 activity by O-GlcNAcylation still remain to be identified.Lire moins >
Langue :
Anglais
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Équipe(s) de recherche :
O-GlcNAcylation, signalisation cellulaire et cycle cellulaire
Date de dépôt :
2020-02-12T15:11:48Z