1. ¹Department of Structural Biology, St Jude Children's Research Hospital, Memphis, TN 38105, USA
2. ²Department of Genetics, Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN 38105, USA

Correspondence: BA Schulman, Department of Structural Biology, MS #311, St Jude Children's Research Hospital, Memphis, TN 38105, USA. E-mail: Brenda.schulman@stjude.org

Abstract

Post-translational covalent attachment of ubiquitin and ubiquitin-like proteins (ubls) has emerged as a predominant cellular regulatory mechanism, with important roles in controlling cell division, signal transduction, embryonic development, endocytic trafficking and the immune response. Ubls function by remodeling the surface of their target proteins, changing their target's half-life, enzymatic activity, protein–protein interactions, subcellular localization or other properties. At least 10 different ubiquitin-like modifications exist in mammals, and attachment of different ubls to a target leads to different biological consequences. Ubl-conjugation cascades are initiated by activating enzymes, which also coordinate the ubls with their downstream pathways. A number of biochemical and structural studies have provided insights into the mechanism of ubl-activating enzymes and their roles in ubl conjugation cascades.