YING-YANG PROTEOMICS: SYSTEMATIC MASS SPECTROMETRY-BASED CHARACTERIZATION OF OGLCNACYLATED AND PHOSPHORYLATED PROTEINS
|Project Members:||Hannes Hahne and Nadine Sobotzki|
O-GlcNAc is an emerging dynamic post-translational modification in eukaryotic cells. O-glycosylation on serine or threonine modulates the activity of nuclear and cytoplasmic proteins and is associated with neurodegenerative pathologies, type II diabetes and several cancers. On so-called yin-yang proteins O-GlcNAc sites are often adjacent to or identical with known phosphosites, thus representing a versatile molecular regulatory mechanism. Despite increasing knowledge on single O-GlcNAc or yin-yang proteins, no method of exists for the large-scale identification of O-GlcNAc proteins and for the concomitant large-scale mapping of O-GlcNAc sites at present.
State-of-the art mass spectrometry-based proteomics provides powerful and flexible tools for the detection and quantification of proteins on a global, system-wide level as well as for the detection and quantification of post-translational protein modifications such divers as phosphorylation, oxidation or proteolytic processing. This work thus focusses on the development of a robust and sensitive mass spectrometry-based technology for the detection and quantification of O-GlcNAc proteins. Among other, the developed technology could find application in revealing dynamics of intracellular signalling events driven by O-GlcNAc glycosylation and phosphorylation, or in clinical studies aiming at the discovery of potential disease biomarkers.