Protein O-GlcNAcylation is a unique glycosylation process in nucleocytoplasm compared to typical glycosylation machinery in ER and Golgi. This is a Ser/Thr-linked O-glycosylation process which is formed with GlcNAc addition through β-O-linkage to serine and threonine residues. Either modification or elongation of O-GlcNAc with other sugars is not further continued in natural states. Thus, O-GlcNAc structure is conserved in high eukaryotes but not established in bacteria and yeast during evolution. Enzymatic catalysis of protein O-GlcNAcylation is exerted by OGT. OGT is known to be essential for cell viability and a single gene encoding OGT produces multiple OGT isoforms in mammalian system. Molecular basis of human OGT has been resolved by crystal structure analyses. During the last two decades, numerous proteins (500 - up to 1000) have been found to contain O-GlcNAc by which they are functioning in various biological processes. Popular aspect of protein O-GlcNAcylation suggests that it can interplay and cross-talk with protein phosphorylation. This concept of protein O-GlcNAcylation comprises of a wide range of cellular events, including signaling cascades, protein interactions, regulation of protein activity, and epigenetic controls. However, it is difficult to clearly define the physiological roles of OGT and O-GlcNAc in vivo primarily because a single enzyme OGT deals with considerable amount of different target proteins and also, within cells, there are combinatorial protein pools of O-GlcNAcylation, frequently together with other post-translational modifications. Here, challenging the multifaceted O-GlcNAc functionality, I present untamed aspects of OGT and O-GlcNAc highlighting hyperthermal sensing and NO regulation.
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