Ubiquitin in the activation and attenuation of innate antiviral immunity

Heaton, Steven M.; Borg, Natalie A.; Dixit, Vishva M.

Ubiquitination is a PTM involving the covalent attachment of the 8.6-kD protein ubiquitin to target proteins. Ubiquitination is catalyzed by the ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin protein ligase (E3). The E3 largely dictates substrate specificity, with at least 617 genes encoding putative ubiquitin and ubiquitin-like E3s annotated in the human genome (Li et al., 2008) . Ubiquitin can undergo ubiquitination itself at its seven lysine residues (K6/K11/K27/K29/K33/K48/K63), building lysine-linked polyubiquitin chains, or its N-terminal methionine (M1), forming linear polyubiquitin chains. Alternatively, ubiquitin chains may be noncovalently associated with target proteins. Furthermore, ubiquitin chains may be remodeled by deubiquitinating enzymes (DUbs; Fig. 1 ). The function, abundance, or subcellular distribution of proteins involved in almost every cellular process is regulated in this way, with an increasingly clear role in regulating innate immunity.