title: Modulation of HSP70 GlcNAc-directed lectin activity by glucose availability and utilization.
abstract: It is well-accepted that protein quality control (occurring either after protein synthesis or after cell damage) is mainly ensured by HSP, but the mechanism by which HSP decides whether the protein will be degraded or not is poorly understood. Within this framework, it has been hypothesized that O-GlcNAc, a cytosolic and nuclear-specific glycosylation whose functions remain unclear, could take a part in the protection of proteins against degradation by modifying both the proteins themselves and the proteasome. Because the synthesis of O-GlcNAc is tightly correlated to glucose metabolism and Hsp70 was endowed with GlcNAc-binding property, we studied the relationship between GlcNAc-binding activity of both Hsp70 and Hsc70 (the nucleocytoplasmic forms of HSP70 family) and glucose availability and utilization. We thus demonstrated that low glucose concentration, inhibition of glucose utilization with 2DG, or inhibition of glucose transport with CytB led to an increase of Hsp70 and Hsc70 lectin activities. Interestingly, the response of Hsp70 and Hsc70 lectin activities toward variations of glucose concentration appeared different: Hsp70 lost its lectin activity when glucose concentration was >5 mM (i.e., physiological glucose concentration) in contrast to Hsc70 that exhibited a maximal lectin activity for glucose concentration approximately 5 mM and at high glucose concentrations. This work also demonstrates that HSP70 does not regulate its GlcNAc-binding properties through its own O-GlcNAc glycosylation.
authors.affiliation: UMR 8576/CNRS, Glycobiologie Structurale et Fonctionnelle, IFR 118, Bâtiment C9, 59655 Villeneuve d'Ascq, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Guinez
authors.forename: Marie-Estelle
authors.initials: ME
authors.lastname: Losfeld
authors.forename: René
authors.initials: R
authors.lastname: Cacan
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Michalski
authors.forename: Tony
authors.initials: T
authors.lastname: Lefebvre
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D046188:Protein Modification, Translational / Q000187:drug effects / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D034781:Receptors, N-Acetylglucosamine / Q000378:metabolism*
chemical_list: D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D034781:Receptors, N-Acetylglucosamine; D046988:Proteasome Endopeptidase Complex; D005947:Glucose