A mutant O-GlcNAcase enriches Drosophila developmental regulators

Autor: Daniel Mariappa, Andrew T. Ferenbach, Daan M. F. van Aalten, Tonia Aristotelous, Matthias Trost, Nithya Selvan, Ritchie Williamson, David G. Campbell, Robert Gourlay, Iva Hopkins-Navratilova
Rok vydání: 2017
Předmět:
Zdroj: Nat Chem Biol
ISSN: 1552-4469
1552-4450
DOI: 10.1038/nchembio.2404
Popis: 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.
Databáze: OpenAIRE