Oral Presentation 28th Annual Lorne Proteomics Symposium 2023

Deciphering the ubiquitin code (#61)

Simon Cobbold 1
  1. Walter and Eliza Hall Institute, Parkville, VIC, Australia

Ubiquitination— the attachment of ubiquitin to a protein substrate—controls almost every process within the cell, and its dysregulation underpins a diversity of inflammatory and neurodegenerative diseases. Ubiquitin can be attached to substrate proteins as a single moiety or as polymeric chains in which successive ubiquitin molecules are connected through specific isopeptide bonds. The complexity of polyubiquitin chains encodes distinct signals within the cell but understanding the substrate repertoire of an E3 ligase or deubiqutinase is non-trivial. Using remnant-ubiquitin enrichment combined with DIA library-free searching we can identify ubiquitination sites putatively regulated by an E3 ligase or deubiquitinase. Combining this approach with Ub-clipping (to define the polyUb chain structure) and Ub-AQUA (to quantify each polyUb linkage abundance) enables a clearer perspective of how the ubiquitin code is written and understood by the cell.