Post-translational modification of proteins with the Ubiquitin-like molecule NEDD8 is a critical regulatory mechanism for several biological processes and a potential target for therapeutic intervention. The role of NEDD8 has been mainly characterised through its modification as single moiety on the cullin family of proteins and control of Cullin-Ring-Ligases, but also on non-cullin substrates. In addition to monoNEDDylation, recent studies have now revealed that NEDD8 can also generate diverse polymers. This is either through modification of the 9 available lysines in NEDD8 and the formation of polyNEDD8 chains, or NEDDylation of Ubiquitin and SUMO-2 for the generation of hybrid NEDD8 chains. Here, we review recent findings that characterise the formation of NEDD8 polymers under distinct modes of protein NEDDylation (canonical/atypical) and their potential role as regulatory signals of the proteotoxic stress response and the Protein Quality Control system.
Keywords: Canonical/atypical NEDDylation; NEDD8 polymers; Protein Quality Control; Proteostasis.
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