O-GlcNAcylation stabilizes β-catenin through ...
Type de document :
Article dans une revue scientifique
DOI :
PMID :
URL permanente :
Titre :
O-GlcNAcylation stabilizes β-catenin through direct competition with phosphorylation at threonine 41
Auteur(s) :
Olivier-Van Stichelen, Stéphanie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Dehennaut, Vanessa [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Buzy, Armelle [Auteur]
Sanofi-Aventis R&D
Zachayus, Jean-Luc [Auteur]
Sanofi-Aventis R&D
Guinez, Celine [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Mir, Anne-Marie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Belkoura, Ikram [Auteur]
null
Copin, Marie-Christine [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Boureme, Didier [Auteur]
Sanofi-Aventis R&D
Loyaux, Denis [Auteur]
Sanofi-Aventis R&D
Ferrara, Pascual [Auteur]
Sanofi-Aventis R&D
Lefebvre, Tony [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Dehennaut, Vanessa [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Buzy, Armelle [Auteur]
Sanofi-Aventis R&D
Zachayus, Jean-Luc [Auteur]
Sanofi-Aventis R&D
Guinez, Celine [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Mir, Anne-Marie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Belkoura, Ikram [Auteur]
null
Copin, Marie-Christine [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Boureme, Didier [Auteur]
Sanofi-Aventis R&D
Loyaux, Denis [Auteur]
Sanofi-Aventis R&D
Ferrara, Pascual [Auteur]
Sanofi-Aventis R&D
Lefebvre, Tony [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Titre de la revue :
The FASEB Journal
Nom court de la revue :
FASEB J.
Numéro :
28
Pagination :
3325-3338
Date de publication :
2014-08
ISSN :
1530-6860
Mot(s)-clé(s) en anglais :
Adenocarcinoma
Enzyme Inhibitors
Phosphorylation
Dietary Carbohydrates
Humans
beta-N-Acetylhexosaminidases
Molecular Sequence Data
Male
Acetylglucosamine
Glucose
Hyperglycemia
Wnt signaling
MCF-7 Cells
Proteolysis
Neoplasm Proteins
HEK293 Cells
Adherens Junctions
Colorectal Neoplasms
Protein Stability
Colon
Wnt Signaling Pathway
Amino Acid Sequence
Intestinal Mucosa
beta Catenin
Threonine
Mice, Inbred C57BL
Glycosylation
N-Acetylglucosaminyltransferases
alpha Catenin
Protein Interaction Mapping
Animals
cancer
Mice
RNA, Small Interfering
Protein Processing, Post-Translational
ETD-MS/MS
Enzyme Inhibitors
Phosphorylation
Dietary Carbohydrates
Humans
beta-N-Acetylhexosaminidases
Molecular Sequence Data
Male
Acetylglucosamine
Glucose
Hyperglycemia
Wnt signaling
MCF-7 Cells
Proteolysis
Neoplasm Proteins
HEK293 Cells
Adherens Junctions
Colorectal Neoplasms
Protein Stability
Colon
Wnt Signaling Pathway
Amino Acid Sequence
Intestinal Mucosa
beta Catenin
Threonine
Mice, Inbred C57BL
Glycosylation
N-Acetylglucosaminyltransferases
alpha Catenin
Protein Interaction Mapping
Animals
cancer
Mice
RNA, Small Interfering
Protein Processing, Post-Translational
ETD-MS/MS
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
Dysfunctions in Wnt signaling increase β-catenin stability and are associated with cancers, including colorectal cancer. In addition, β-catenin degradation is decreased by nutrient-dependent O-GlcNAcylation. Human colon ...
Lire la suite >Dysfunctions in Wnt signaling increase β-catenin stability and are associated with cancers, including colorectal cancer. In addition, β-catenin degradation is decreased by nutrient-dependent O-GlcNAcylation. Human colon tumors and colons from mice fed high-carbohydrate diets exhibited higher amounts of β-catenin and O-GlcNAc relative to healthy tissues and mice fed a standard diet, respectively. Administration of the O-GlcNAcase inhibitor thiamet G to mice also increased colonic expression of β-catenin. By ETD-MS/MS, we identified 4 O-GlcNAcylation sites at the N terminus of β-catenin (S23/T40/T41/T112). Furthermore, mutation of serine and threonine residues within the D box of β-catenin reduced O-GlcNAcylation by 75%. Interestingly, elevating O-GlcNAcylation in human colon cell lines drastically reduced phosphorylation at T41, a key residue of the D box responsible for β-catenin stability. Analyses of β-catenin O-GlcNAcylation mutants reinforced T41 as the most crucial residue that controls the β-catenin degradation rate. Finally, inhibiting O-GlcNAcylation decreased the β-catenin/α-catenin interaction necessary for mucosa integrity, whereas O-GlcNAcase silencing improved this interaction. These results suggest that O-GlcNAcylation regulates not only the stability of β-catenin, but also affects its localization at the level of adherens junctions. Accordingly, we propose that O-GlcNAcylation of β-catenin is a missing link between the glucose metabolism deregulation observed in metabolic disorders and the development of cancer.Lire moins >
Lire la suite >Dysfunctions in Wnt signaling increase β-catenin stability and are associated with cancers, including colorectal cancer. In addition, β-catenin degradation is decreased by nutrient-dependent O-GlcNAcylation. Human colon tumors and colons from mice fed high-carbohydrate diets exhibited higher amounts of β-catenin and O-GlcNAc relative to healthy tissues and mice fed a standard diet, respectively. Administration of the O-GlcNAcase inhibitor thiamet G to mice also increased colonic expression of β-catenin. By ETD-MS/MS, we identified 4 O-GlcNAcylation sites at the N terminus of β-catenin (S23/T40/T41/T112). Furthermore, mutation of serine and threonine residues within the D box of β-catenin reduced O-GlcNAcylation by 75%. Interestingly, elevating O-GlcNAcylation in human colon cell lines drastically reduced phosphorylation at T41, a key residue of the D box responsible for β-catenin stability. Analyses of β-catenin O-GlcNAcylation mutants reinforced T41 as the most crucial residue that controls the β-catenin degradation rate. Finally, inhibiting O-GlcNAcylation decreased the β-catenin/α-catenin interaction necessary for mucosa integrity, whereas O-GlcNAcase silencing improved this interaction. These results suggest that O-GlcNAcylation regulates not only the stability of β-catenin, but also affects its localization at the level of adherens junctions. Accordingly, we propose that O-GlcNAcylation of β-catenin is a missing link between the glucose metabolism deregulation observed in metabolic disorders and the development of cancer.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
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
2021-07-13T06:41:44Z
2021-07-13T06:41:44Z