Ataxin-10 interacts with O-linked beta-N-acetylglucosamine transferase in the brain - PubMed (original) (raw)
. 2006 Jul 21;281(29):20263-70.
doi: 10.1074/jbc.M601563200. Epub 2006 May 18.
Jörg Stetefeld, Kerstin Bendfeldt, Cordula Nitsch, Jochen Reinstein, Robert L Shoeman, Beatrice Dimitriades-Schmutz, Martine Schwager, Dominic Leiser, Sabire Ozcan, Uwe Otten, Suat Ozbek
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- PMID: 16714295
- DOI: 10.1074/jbc.M601563200
Free article
Ataxin-10 interacts with O-linked beta-N-acetylglucosamine transferase in the brain
Pia März et al. J Biol Chem. 2006.
Free article
Abstract
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.
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