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Although the knowledge that nuclear and cytoplasmic proteins are modified with N-acetylglucosamine …


Biology Articles » Biochemistry » Enzymology » Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development

Abstract
- Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development

Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development

Thomas R. Whisenhunt2,3, Xiaoyong Yang6, Damon B. Bowe4, Andrew J. Paterson5, Brian A. Van Tine3 and Jeffrey E. Kudlow1,2,4,5

2 Department of Cell Biology, 3 Medical Scientist Training Program, 4 Department of Pharmacology and Toxicology, and 5 Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; and 6Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037

An open access article from Glycobiology 2006 16(6):551-563. Originally published by Oxford University Press.  

 

Abstract

Although the knowledge that nuclear and cytoplasmic proteinsare modified with N-acetylglucosamine has existed for decades,little has been shown as to its function until recently. Thereare now substantial data highlighting the significance of properregulation of this modification in multiple cellular processes.Currently, only two enzymes are known that regulate this modification.O-GlcNAc transferase (OGT) modifies protein substrates posttranslationallyby adding the N-acetylglucosamine. Bifunctional nuclear/cytoplasmicO-GlcNAcase and acetyl transferase (NCOAT) is responsible forcleaving the modification from target proteins. Here, we demonstratefor the first time an unusual association of these two opposingenzymes into a single O-GlcNAczyme complex. NCOAT and OGT associatestrongly through specific domains such that NCOAT accompaniesOGT, with histone deacetylases (HDACs), into transcription corepressioncomplexes. Exclusion of NCOAT activities from OGT associationblocks proper estrogen-dependent cell signaling as well as mammarydevelopment in transgenic mice. This demonstrates that NCOATis in a strategic position to rapidly counteract OGT and HDACwithout requiring its recruitment.

Key words: corepressor / estrogen / HAT / O-GlcNAcase / OGT

 


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