Ubiquitin and ubiquitin-like proteins as multifunctional signals

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Abstract
Protein ubiquitylation is a recognized signal for protein degradation. The covalent linkage of a K48-linked polyubiquitin chain to a target protein signals its degradation by the 26S proteasome. It is increasingly realized that ubiquitin conjugation to proteins can be used for many other non-degradative purposes. For example, monoubiquitylation can induce receptor-mediated endocytosis and receptor sorting into multivesicular bodies, and K63-linked polyubiquitin chains can function in signal-transduction cascades. Furthermore, there are many ubiquitin-like proteins that can be conjugated to various proteins to control their activities. All of these ubiqutin-like proteins are characterized by the ubiquitin superfold, despite the fact that some of them have little or no sequence homology to ubiquitin. The ubiquitin superfold can also be genetically built into larger proteins, where it can function to regulate various downstream processes. We currently know about only a small number of the proteins that are modified by ubiquitin and ubiquitin-like proteins (ubiquitons). With modern proteomics, we expect to find that many regulatory proteins are conjugated to ubiquitons to enhance the specificity of protein interactions.