Abstract
As originally described some 40 years ago, protein ubiquitination was thought to serve primarily as a static mark for protein degradation. In the ensuing years, it has become clear that 'ubiquitination' is a structurally diverse and dynamic post-translational modification and is intricately involved in a myriad of signaling pathways in all eukaryote cells. And like other key pathways in the functional proteome, ubiquitin signaling is often disrupted, sometimes severely so, in human pathophysiology. As a result of its central role in normal physiology and human disease, the ubiquitination field is now represented across the full landscape of biomedical research from fundamental structural and biochemical studies to translational and clinical research. In recent years, mass spectrometry has emerged as a powerful technology for the detection and characterization of protein ubiquitination. Herein we detail qualitative and quantitative proteomic methods using a compare/contrast approach to highlight their strengths and weaknesses.