Hsp70-GlcNAc-binding activity is released by stress, proteasome inhibition, and protein misfolding.

Céline Guinez (1) , Anne-Marie Mir (1) , Yves Leroy (1) , René Cacan (1) , Jean-Claude Michalski (1) , Tony Lefebvre (1)

1 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576

Numerous recent works strengthen the idea that the nuclear and cytosolic-specific O-GlcNAc glycosylation protects cells against injuries. We have first investigated O-GlcNAc level and Hsp70-GlcNAc-binding activity (HGBA) behaviour after exposure of HeLa and HepG(2) cells to a wide variety of stresses. O-GlcNAc and HGBA responses were different according to the stress and according to the cell. HGBA was released for almost all stresses, while O-GlcNAc level was modified either upwards or downwards, depending to the stress. Against all expectations, we demonstrated that energy charge did not significantly vary with stress whereas UDP-GlcNAc pools were more dramatically affected even if differences in UDP-GlcNAc contents were not correlated with O-GlcNAc variations suggesting that O-GlcNAc transferase is itself finely regulated during cell injury. Finally, HGBA could be triggered by proteasome inhibition and by L-azetidine-2-carboxylic acid (a proline analogue) incorporation demonstrating that protein misfolding is one of the key-activator of this Hsp70 property.

Domaines: Biochimie [q-bio.BM]

Céline Guinez, Anne-Marie Mir, Yves Leroy, René Cacan, Jean-Claude Michalski, et al.. Hsp70-GlcNAc-binding activity is released by stress, proteasome inhibition, and protein misfolding.. Biochemical and Biophysical Research Communications, 2007, 361 (2), pp.414-420. ⟨hal-00250045⟩