Selvan, N., Williamson, R., Mariappa, D., Campbell, D.G., Gourlay, R., Ferenbach, A.T., Aristotelous, T., Hopkins-Navratilova, I., Trost, M., van Aalten, D.M.F. (2017). A mutant O-GlcNAcase enriches Drosophila developmental regulators.  Nat. Chem. Biol. 13(8): 882--887.

FBrf0236524

Research paper

Protein O-GlcNAcylation is a reversible post-translational modification of serines and threonines on nucleocytoplasmic proteins. It is cycled by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (O-GlcNAcase or OGA). Genetic approaches in model organisms have revealed that protein O-GlcNAcylation is essential for early embryogenesis. The Drosophila melanogaster gene supersex combs (sxc), which encodes OGT, is a polycomb gene, whose null mutants display homeotic transformations and die at the pharate adult stage. However, the identities of the O-GlcNAcylated proteins involved and the underlying mechanisms linking these phenotypes to embryonic development are poorly understood. Identification of O-GlcNAcylated proteins from biological samples is hampered by the low stoichiometry of this modification and by limited enrichment tools. Using a catalytically inactive bacterial O-GlcNAcase mutant as a substrate trap, we have enriched the O-GlcNAc proteome of the developing Drosophila embryo, identifying, among others, known regulators of Hox genes as candidate conveyors of OGT function during embryonic development.

PMC7611224 (PMC) (EuropePMC)