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Review
. 2013 Aug;45(8):1833-42.
doi: 10.1016/j.biocel.2013.05.026. Epub 2013 May 31.

Non-canonical ubiquitylation: mechanisms and consequences

Gary S McDowell  1 , Anna Philpott
Affiliations
Free article
Review

Non-canonical ubiquitylation: mechanisms and consequences

Gary S McDowell et al. Int J Biochem Cell Biol. 2013 Aug.
Free article

Abstract

Post-translational protein modifications initiate, regulate, propagate and terminate a wide variety of processes in cells, and in particular, ubiquitylation targets substrate proteins for degradation, subcellular translocation, cell signaling and multiple other cellular events. Modification of substrate proteins is widely observed to occur via covalent linkages of ubiquitin to the amine groups of lysine side-chains. However, in recent years several new modes of ubiquitin chain attachment have emerged. For instance, covalent modification of non-lysine sites in substrate proteins is theoretically possible according to basic chemical principles underlying the ubiquitylation process, and evidence is building that sites such as the N-terminal amine group of a protein, the hydroxyl group of serine and threonine residues and even the thiol groups of cysteine residues are all employed as sites of ubiquitylation. However, the potential importance of this "non-canonical ubiquitylation" of substrate proteins on sites other than lysine residues has been largely overlooked. This review aims to highlight the unusual features of the process of non-canonical ubiquitylation and the consequences of these events on the activity and fate of a protein.

Keywords: ERAD; HECT; HOMO; LUMO; Non-canonical ubiquitylation; Protein degradation; RING; SCF; SUMO; Skp-Cullin-F-box; UFD; UPS; Ub; Ubiquitin; Ubiquitin ligase; Ubiquitinomics; endoplasmic reticulum-associated degradation; highest occupied molecular orbital; homologous to E6 carboxyl terminus; lowest unoccupied molecular orbital; really Interesting New Gene; small ubiquitin-like modifier; ubiquitin; ubiquitin fusion degradation; ubiquitin proteasome system.

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