Title :

Proteomics and PUGNAcity will overcome questioning of insulin resistance induction by nonselective inhibition of O-GlcNAcase

Author(s) :

Dehennaut, Vanessa [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Lefebvre, Tony [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]

Journal title :

Proteomics

Abbreviated title :

Proteomics

Volume number :

13

Pages :

2944-2946

Publication date :

2013-10

ISSN :

1615-9861

English keyword(s) :

Oximes
Humans
Phenylcarbamates
beta-N-Acetylhexosaminidases
Insulin Resistance
Acetylglucosamine
Glycosylation
Hexosaminidases inhibitors
3T3-L1 Cells
Hep G2 Cells
Ubiquitination
Animals
Biomedicine
Chromatography, Affinity
Proteomics
O-GlcNAcylation
Mice
PUGNAc
Insulin signaling

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

PTMs are the ultimate elements that perfect the existence and the activity of proteins. Owing to PTM, not less than 500 millions biological activities arise from approximately 20 000 protein-coding genes in human. Hundreds ...
Show more >PTMs are the ultimate elements that perfect the existence and the activity of proteins. Owing to PTM, not less than 500 millions biological activities arise from approximately 20 000 protein-coding genes in human. Hundreds of PTM were characterized in living beings among which is a large variety of glycosylations. Many compounds have been developed to tentatively block each kind of glycosylation so as to study their biological functions but due to their complexity, many off-target effects were reported. Insulin resistance exemplifies this problem. Several independent groups described that inhibiting the removal of O-GlcNAc moieties using O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), a nonselective inhibitor of the nuclear and cytoplasmic O-GlcNAcase, induced insulin resistance both in vivo and ex vivo. The development of potent and highly selective O-GlcNAcase inhibitors called into question that elevated O-GlcNAcylation levels are responsible for insulin resistance; these compounds not recapitulating the insulin-desensitizing effect of PUGNAc. To tackle this intriguing problem, a South Korean group recently combined ATP-affinity chromatography and gel-assisted digestion to identify proteins, differentially expressed upon treatment of 3T3-L1 adipocytes with PUGNAc, involved in protein turnover and insulin signaling.Show less >

Language :

Anglais

Audience :

Non spécifiée

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161
• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

O-GlcNAcylation, signalisation cellulaire et cycle cellulaire

Submission date :

2020-02-12T15:11:53Z
2021-03-18T12:56:50Z