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Mixed in chains: NEDD8 polymers in the Protein Quality Control system
Igor Meszka1, Jolanta Polanowska1, Dimitris P Xirodimas1
1CRBM, Univ. Montpellier, CNRS, Montpellier, France.
Seminars in Cell & Developmental Biology
|January 26, 2022
Summary
Ubiquitin-like molecule NEDD8 modifies proteins, regulating biological processes. New research reveals NEDD8 can form diverse polymers, impacting proteotoxic stress and protein quality control systems.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Post-translational modification with NEDD8 is crucial for biological regulation and therapeutics.
- NEDD8 primarily modifies cullin proteins, controlling Cullin-Ring-Ligases, but also affects non-cullin substrates.
- Beyond single modifications, NEDD8 can form diverse polymers.
Purpose of the Study:
- To review recent findings on the formation of NEDD8 polymers.
- To characterize distinct modes of protein NEDDylation (canonical/atypical) leading to polymer formation.
- To explore the potential role of NEDD8 polymers in proteotoxic stress response and Protein Quality Control.
Main Methods:
- Literature review of recent findings on NEDD8 polymerization.
- Analysis of distinct NEDDylation modes (mono- vs. poly-).
- Investigation of NEDD8 polymer formation via polyNEDD8 and hybrid chains.
Main Results:
- NEDD8 can form polyNEDD8 chains by modifying its own lysines.
- Hybrid chains are formed by NEDDylating Ubiquitin and SUMO-2.
- These polymerization events occur under both canonical and atypical NEDDylation.
- NEDD8 polymers are implicated in regulating proteotoxic stress and protein quality control.
Conclusions:
- NEDD8 polymerization represents a novel regulatory mechanism.
- Understanding NEDD8 polymer formation is key to elucidating its role in cellular stress responses.
- This highlights new therapeutic avenues targeting NEDD8 pathways.
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