Tony Lefebvre

ORCID: 0000-0001-9883-2240
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About
Contact & Profiles
Research Areas
  • Glycosylation and Glycoproteins Research
  • Galectins and Cancer Biology
  • Carbohydrate Chemistry and Synthesis
  • RNA modifications and cancer
  • Ubiquitin and proteasome pathways
  • Lysosomal Storage Disorders Research
  • Cancer, Lipids, and Metabolism
  • Heat shock proteins research
  • Wnt/β-catenin signaling in development and cancer
  • Endoplasmic Reticulum Stress and Disease
  • Genomics and Chromatin Dynamics
  • Metabolism, Diabetes, and Cancer
  • Cellular transport and secretion
  • Microtubule and mitosis dynamics
  • RNA and protein synthesis mechanisms
  • Caveolin-1 and cellular processes
  • Algal biology and biofuel production
  • Reproductive Biology and Fertility
  • Microbial Community Ecology and Physiology
  • Polyamine Metabolism and Applications
  • Diet, Metabolism, and Disease
  • Protein Structure and Dynamics
  • Cholesterol and Lipid Metabolism
  • Animal Genetics and Reproduction
  • Epigenetics and DNA Methylation

Centre National de la Recherche Scientifique
2015-2024

Université de Lille
2014-2024

Unité de Glycobiologie Structurale et Fonctionnelle
2015-2024

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2020-2024

Centre National pour la Recherche Scientifique et Technique (CNRST)
2004-2014

Laboratoire de Chimie
2001-2013

University of Minnesota Medical Center
2007

Institut de Biologie de Lille
2004

Institut Pasteur de Lille
2004

École Nationale Supérieure de Chimie de Lille
2000-2003

O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification consisting in the addition of sugar moiety to serine/threonine residues cytosolic or nuclear proteins. Catalyzed by O-GlcNAc-transferase (OGT) and removed O-GlcNAcase, this dynamic dependent on environmental glucose concentration. O-GlcNAcylation regulates activities wide panel proteins involved almost all aspects cell biology. As nutrient sensor, can relay effects excessive nutritional...

10.3389/fendo.2013.00099 article EN cc-by Frontiers in Endocrinology 2013-01-01

Carbohydrate-responsive element-binding protein (ChREBP) is a key transcription factor that mediates the effects of glucose on glycolytic and lipogenic genes in liver. We have previously reported liver-specific inhibition ChREBP prevents hepatic steatosis ob/ob mice by specifically decreasing rates vivo. To better understand regulation activity liver, we investigated implication O-linked β-N-acetylglucosamine (O-GlcNAc or O-GlcNAcylation), an important glucose-dependent posttranslational...

10.2337/db10-0452 article EN cc-by-nc-nd Diabetes 2011-04-07

Dysfunctions in Wnt signaling increase β-catenin stability and are associated with cancers, including colorectal cancer. In addition, degradation is decreased by nutrient-dependent O-GlcNAcylation. Human colon tumors colons from mice fed high-carbohydrate diets exhibited higher amounts of O-GlcNAc relative to healthy tissues a standard diet, respectively. Administration the O-GlcNAcase inhibitor thiamet G also increased colonic expression β-catenin. By ETD-MS/MS, we identified 4...

10.1096/fj.13-243535 article EN The FASEB Journal 2014-04-17

During the past two decades, O-GlcNAc modification of cytosolic and nuclear proteins has been intensively studied. Nevertheless, function this post-translational remains unclear. It recently speculated that could act as a protective signal against proteasomal degradation, both by modifying target substrates and/or inhibiting proteasome itself. In work, we have investigated putative relation between ubiquitin pathway. First, showed level modifications increased rapidly after thermal stress...

10.1096/fj.07-102509 article EN The FASEB Journal 2008-04-23

O-linked N-acetylglucosaminylation (O-GlcNAc) is a regulatory post-translational modification of nucleo-cytoplasmic proteins that has complex interplay with phosphorylation. O-GlcNAc been described as nutritional sensor, the level UDP-GlcNAc serves donor for uridine diphospho-N-acetylglucosamine:polypeptide beta-N-acetyl-glucosaminyltransferase being regulated by cellular fate glucose. Because muscular contraction both dependent on glucose metabolism and highly...

10.1074/mcp.m400024-mcp200 article EN cc-by Molecular & Cellular Proteomics 2004-03-02

O-Linked N-acetylglucosaminylation (O-GlcNAcylation) (or O-linked N-acetylglucosamine (O-GlcNAc)) is an abundant and reversible glycosylation type found within the cytosolic nuclear compartments. We have described previously sudden O-GlcNAcylation increase occurring during Xenopus laevis oocyte G2/M transition, we demonstrated that inhibition of O-GlcNAc-transferase (OGT) blocked this process, showing dynamism interferes with cell cycle progression. In work, identified proteins are...

10.1074/mcp.m700494-mcp200 article EN cc-by Molecular & Cellular Proteomics 2008-07-11

The short half-life protooncogene β-catenin acquires a remarkable stability in large subset of cancers, mainly from mutations affecting its proteasomal degradation. In this sense, colorectal cancers (CRC) form group pathologies which early steps development are characterized by an aberrant expression and uncontrolled proliferation epithelial cells. Diet has long been described as influence the emergence CRC, but molecular events that link metabolic disorders CRC remain elusive. Part...

10.1152/ajpendo.00390.2011 article EN AJP Endocrinology and Metabolism 2011-11-23

Bile acid metabolism is intimately linked to the control of energy homeostasis and glucose lipid metabolism. The nuclear receptor farnesoid X (FXR) plays a major role in enterohepatic cycling bile acids, but impact nutrients on poorly characterized. Metabolically active hepatocytes cope with increases intracellular concentrations by directing into storage (glycogen) or oxidation (glycolysis) pathways, as well pentose phosphate shunt hexosamine biosynthetic pathway. Here we studied whether...

10.1002/hep.26710 article EN Hepatology 2013-08-28

The post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is regulated a unique couple enzymes. O-GlcNAc transferase (OGT) transfers the GlcNAc residue from UDP-GlcNAc, final product hexosamine biosynthetic pathway (HBP), whereas O-GlcNAcase (OGA) removes it. This study and others show that OGT O-GlcNAcylation levels are increased in cancer cell lines. In context we studied effect silencing colon lines HT29 HCT116 primary line CCD841CoN. Herein report...

10.3389/fendo.2016.00046 article EN cc-by Frontiers in Endocrinology 2016-05-25

Full-grown <i>Xenopus</i> oocytes are arrested at the prophase of first meiotic division in a G<sub>2</sub>-like state. Progesterone triggers resumption also called G<sub>2</sub>/M transition. This event is characterized by germinal vesicle breakdown (GVBD) and burst phosphorylation level that reflects activation M-phase-promoting factor (MPF) MAPK pathways. Besides ubiquitin pathways, increasing evidence has suggested cytosolic nucleus-specific <i>O</i>-GlcNAc glycosylation contributes to...

10.1074/jbc.m700444200 article EN cc-by Journal of Biological Chemistry 2007-03-01

Nuclear and cytoplasmic O-GlcNAc transferase (OGT) is a unique universally expressed enzyme catalyzing O-GlcNAcylation of thousands proteins. Although OGT interferes with many crucial intracellular processes, including cell cycle, only few studies have focused on elucidating the precise role glycosyltransferase during cycle entry. We first demonstrated that starved MCF7 cells reincubated serum quickly induced significant increase concomitantly to activation PI3K MAPK pathways....

10.1038/oncsis.2012.36 article EN cc-by Oncogenesis 2012-12-10

Lipid microdomains (rafts) are cholesterol-enriched dynamic ordered lipid domains belonging to cell membranes involved in diverse cellular functions, including signal transduction, membrane trafficking, and infection. Many studies have reported relationships between insulin signaling rafts. Likewise, links O-GlcNAcylation also been described. However, the potential connection O-GlcNAc raft dynamics remains unexplored. Here we show that enzyme creates this modification, transferase (OGT),...

10.1096/fj.12-217984 article EN The FASEB Journal 2013-05-20

Significance Using an interactomic approach, we have identified the nuclear receptor REV-ERBα as a O-GlcNAc transferase (OGT) protein partner. protects cytoplasmic OGT from proteasomal degradation and facilitates cytosolic O-GlcNAcylation while REV-ERα ligands decreased activity. thus exerts pleiotropic activities through OGT, coordinating signal transduction, epigenomic programming, transcriptional response in liver.

10.1073/pnas.1805397115 article EN cc-by-nc-nd Proceedings of the National Academy of Sciences 2018-11-05

Adipocyte differentiation and function relies on a network of transcription factors, which is disrupted in obesity-associated low grade, chronic inflammation leading to adipose tissue dysfunction. In this context, there need for thorough understanding the transcriptional regulatory involved pathophysiology. Recent advances functional annotation genome has highlighted role non-coding RNAs cellular processes coordination with factors. Using an unbiased genome-wide approach, we identified...

10.1038/s41598-017-14570-y article EN cc-by Scientific Reports 2017-10-20
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