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Ataxin-10 Interacts with O-Linked β-N-Acetylglucosamine Transferase in the Brain

2006; Elsevier BV; Volume: 281; Issue: 29 Linguagem: Inglês

10.1074/jbc.m601563200

1083-351X

Pia März, Jörg Stetefeld, Kerstin Bendfeldt, Cordula Nitsch, Jochen Reinstein, Robert L. Shoeman, Beatrice Dimitriades‐Schmutz, Martine Schwager, Dominic Leiser, Sabire Özcan, U. Otten, Suat Özbek,

Carbohydrate Chemistry and Synthesis

Modification by O-GlcNAc involves a growing number of eucaryotic nuclear and cytosolic proteins. Glycosylation of intracellular proteins is a dynamic process that in several cases competes with and acts as a reciprocal modification system to phosphorylation. O-Linked beta-N-acetylglucosamine transferase (OGT) levels are highest in the brain, and neurodegenerative disorders such as Alzheimer disease have been shown to involve abnormally phosphorylated key proteins, probably as a result of hypoglycosylation. Here, we show that the neurodegenerative disease protein ataxin-10 (Atx-10) is associated with cytoplasmic OGT p110 in the brain. In PC12 cells and pancreas, this association is competed by the shorter OGT p78 splice form, which is down-regulated in brain. Overexpression of Atx-10 in PC12 cells resulted in the reconstitution of the Atx-10-OGT p110 complex and enhanced intracellular glycosylation activity. Moreover, in an in vitro enzyme assay using PC12 cell extracts, Atx-10 increased OGT activity 2-fold. These data indicate that Atx-10 might be essential for the maintenance of a critical intracellular glycosylation level and homeostasis in the brain.