A mutant O-GlcNAcase enriches Drosophila developmental regulators

TY - JOUR

T1 - A mutant O-GlcNAcase enriches Drosophila developmental regulators

AU - Selvan, Nithya

AU - Williamson, Ritchie

AU - Mariappa, Daniel

AU - Campbell, David G.

AU - Gourlay, Robert

AU - Ferenbach, Andrew T.

AU - Aristotelous, Tonia

AU - Hopkins-Navratilova, Iva

AU - Trost, Matthias

AU - van Aalten, Daan M. F.

N1 - This work is funded by a Wellcome Trust Senior Investigator Award (110061) to D.M.F.v.A. M.T. is funded by a MRC grant (MC_UU_12016/5). R.W. is funded by a Royal Society Research Grant.

PY - 2017/8

Y1 - 2017/8

N2 - 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.

AB - 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.

KW - Chemical tools

KW - Glycobiology

KW - Glycomics

KW - Post-translational modifications

U2 - 10.1038/nchembio.2404

DO - 10.1038/nchembio.2404

M3 - Article

C2 - 28604694

SN - 1552-4450

VL - 13

SP - 882

EP - 887

JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 8

ER -