Review
Non-canonical ubiquitylation: Mechanisms and consequences

https://doi.org/10.1016/j.biocel.2013.05.026Get rights and content
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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.

Abbreviations

Ub
ubiquitin
SCF
Skp-Cullin-F-box
HECT
homologous to E6 carboxyl terminus
RING
really Interesting New Gene
SUMO
small ubiquitin-like modifier
UPS
ubiquitin proteasome system
UFD
ubiquitin fusion degradation
ERAD
endoplasmic reticulum-associated degradation
HOMO
highest occupied molecular orbital
LUMO
lowest unoccupied molecular orbital

Keywords

Non-canonical ubiquitylation
Ubiquitin
Protein degradation
Ubiquitinomics
Ubiquitin ligase

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