Glycobiology Advance Access originally published online on September 21, 2005
Glycobiology 2006 16(1):22-28; doi:10.1093/glycob/cwj041
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Modulation of HSP70 GlcNAc-directed lectin activity by glucose availability and utilization
UMR 8576/CNRS, Glycobiologie Structurale et Fonctionnelle, IFR 118, Bâtiment C9, 59655 Villeneuve d’Ascq, France
1 To whom correspondence should be addressed; e-mail: tony.lefebvre{at}univ-lille1.fr
Received on May 4, 2005; revised on September 7, 2005; accepted on September 14, 2005
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 ~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.
Key words: glucose / heat shock proteins / hexosamine biosynthetic pathway / lectin / O-GlcNAc
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