Decoding Ubiquitin Modifications by Mass Spectrometry

Protein ubiquitination is a critical and widely distributed post-translational modification (PTM) involved in the regulation of almost every cellular process and pathway in cells, such as proteostasis, DNA repair, trafficking, and immunity. Mass spectrometry (MS)-based proteomics is a robust tool to decode the complexity of ubiquitin networks by disclosing the proteome-wide ubiquitination sites, the length, linkage and topology of ubiquitin chains, the chemical modification of ubiquitin chains, and the crosstalk between ubiquitination and other PTMs. In this chapter, we discuss the application of MS in the interpretation of the ubiquitin code.