O-linked N-acetylglucosamine suppresses thermal aggregation of Sp1

We demonstrate that O-linked N-acetylglucosamine (O-GlcNAc), a ubiquitous protein modification in eukaryotes, suppresses thermal inactivation of Sp1 transcription factor. 6-Diazo-5-oxonorleucine treatment or O-GlcNAcase overexpression, which reduced O-GlcNAc levels on Sp1, deteriorated thermal stability of Sp1 and O-GlcNAc modified molecules of Sp1 resist thermal aggregation in vitro. We also showed that heat-induced elevation of heat shock protein 70 was facilitated by Sp1 but blunted under low O-GlcNAc levels, suggesting that O-GlcNAc might upregulate the expression of heat shock protein 70 through thermoprotection of Sp1, which eventually enhanced cellular thermotolerance. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.