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A lipid-droplet-targeted O-GlcNAcase isoform is a key regulator of the proteasome

Keembiyehetty, Chithra N., Krzeslak, Anna, Love, Dona C., Hanover, John A.·2011·Journal of Cell Science
DOI 10.1242/jcs.083287
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Abstract

Protein-O-linked N-Acetyl-β-D-glucosaminidase (O-GlcNAcase, OGA; also known as hexosaminidase C) participates in a nutrient-sensing, hexosamine signaling pathway by removing O-linked N-acetylglucosamine (O-GlcNAc) from key target proteins. Perturbations in O-GlcNAc signaling have been linked to Alzheimer's disease, diabetes and cancer. Mammalian O-GlcNAcase exists as two major spliced isoforms differing only by the presence (OGA-L) or absence (OGA-S) of a histone-acetyltransferase domain. Here we demonstrate that OGA-S accumulates on the surface of nascent lipid droplets with perilipin-2; both of these proteins are stabilized by proteasome inhibition. We show that selective downregulation of OGA-S results in global proteasome inhibition and the striking accumulation of ubiquitinylated proteins. OGA-S knockdown increased levels of perilipin-2 and perilipin-3 suggesting that O-GlcNAc-dependent regulation of proteasomes might occur on the surface of lipid droplets. By locally activating proteasomes during maturation of the nascent lipid droplet, OGA-S could participate in an O-GlcNAc-dependent feedback loop regulating lipid droplet surface remodeling. Our findings therefore suggest a mechanistic link between hexosamine signaling and lipid droplet assembly and mobilization.

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Metadata

Authors
Keembiyehetty, C. N., Krzeslak, A., Love, D. C., & Hanover, J. A.
Affiliations
Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Kidney Diseases, National Institute of Health, Bethesda, MD 20892, USA
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2011-08-15
Volume
124
Issue
16
Pages
2851-2860
ISSN
  • 1477-9137
  • 0021-9533
DOI
10.1242/jcs.083287
Cited by
109
References
1
Language
en

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CoChat. (2026). Citation check: A lipid-droplet-targeted O-GlcNAcase isoform is a key regulator of the proteasome. https://app.cochat.ai/papers/10.1242/jcs.083287
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Keembiyehetty, C. N., Krzeslak, A., Love, D. C., & Hanover, J. A. (2011). A lipid-droplet-targeted O-GlcNAcase isoform is a key regulator of the proteasome. Journal of Cell Science. https://doi.org/10.1242/jcs.083287