A mutant O-GlcNAcase enriches Drosophila developmental regulators

Nithya Selvan, Ritchie Williamson, Daniel Mariappa, David G. Campbell, Robert Gourlay, Andrew T. Ferenbach, Tonia Aristotelous, Iva Hopkins-Navratilova, Matthias Trost, Daan M. F. van Aalten (Lead / Corresponding author)

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Abstract

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.

Original languageEnglish
Pages (from-to)882-887
Number of pages8
JournalNature Chemical Biology
Volume13
Issue number8
Early online date12 Jun 2017
DOIs
Publication statusPublished - Aug 2017

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Keywords

  • Chemical tools
  • Glycobiology
  • Glycomics
  • Post-translational modifications

Cite this

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. Nature Chemical Biology, 13(8), 882-887. https://doi.org/10.1038/nchembio.2404