O-GlcNAc Transferase (OGT) is an essential glycosyltransferase that catalyzes the attachment of N-acetylglucosamine (GlcNAc) to serines and threonines of numerous nuclear and cytoplasmic proteins.  Global O-GlcNAcylation levels increase with increased flux through the hexosamine biosynthetic pathway, which produces OGT's donor substrate, UDP-GlcNAc.  Increased O-GlcNAcylation is associated with widespread changes in gene expression, but the molecular mechanisms underlying these changes remain poorly understood.  It was recently reported that OGT catalyzes another post-translational modification: the cleavage of host cell factor 1 (HCF-1), a ubiquitous transcriptional coregulator found in several chromatin remodeling complexes.  We will describe studies confirming that OGT has proteolytic activity and showing that HCF-1 cleavage occurs in the same active site as glycosylation.  Based on structural work and biochemistry, a novel mechanism for proteolysis is proposed.

Split personality of O-GlcNAc transferase

247th National Meeting (2014)

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