The emerging complexity of protein ubiquitination
Abstract
Protein ubiquitination and protein phosphorylation are two fundamental regulatory post-translational modifications controlling intracellular signalling events. However, the ubiquitin system is vastly more complex compared with phosphorylation. This is due to the ability of ubiquitin to form polymers, i.e. ubiquitin chains, of at least eight different linkages. The linkage type of the ubiquitin chain determines whether a modified protein is degraded by the proteasome or serves to attract proteins to initiate signalling cascades or be internalized. The present review focuses on the emerging complexity of the ubiquitin system. I review what is known about individual chain types, and highlight recent advances that explain how the ubiquitin system achieves its intrinsic specificity. There is much to be learnt from the better-studied phosphorylation system, and many key regulatory mechanisms underlying control by protein phosphorylation may be similarly employed within the ubiquitin system. For example, ubiquitination may have important allosteric roles in protein regulation that are currently not appreciated.
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Ubiquitination is achieved through the hierarchical action of three enzymes: E1, E2, and E3.
“Ubiquitination, the key step in targeting a protein for proteasomal degradation, is achieved through the hierarchical action of three enzymes, termed ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (Ubc or E2), and ubiquitin ligase (E3) (7, 8).”
From RNF170 Protein, an Endoplasmic Reticulum Membrane Ubiquitin Ligase, Mediates Inositol 1,4,5-Trisphosphate Receptor Ubiquitination and Degradation (2011) · cites this paper as [8]
The generally accepted summary of the UPP is that substrates are first polyubiquitinated and then processed by the proteasome.
“The generally accepted summary of the UPP is that substrates are first polyubiquitinated and then processed by the proteasome, a multi-subunit protease that can recognize and degrade polyubiquitinated proteins (7, 8).”
From RNF170 Protein, an Endoplasmic Reticulum Membrane Ubiquitin Ligase, Mediates Inositol 1,4,5-Trisphosphate Receptor Ubiquitination and Degradation (2011) · cites this paper as [8]
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- Authors
- Komander, D.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Komander, David
- ORCID
- Komander, David
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2009-09-21
- Volume
- 37
- Issue
- 5
- Pages
- 937-953
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- OpenAlex
- W2115416706
- Cited by
- 821
- References
- 4
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 45 · 2023: 41 · 2022: 47 · 2021: 57 · 2020: 35 · 2019: 35 · 2018: 42 · 2017: 60 · 2016: 55 · 2015: 63 · 2014: 74 · 2013: 50 · 2012: 71
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Society Transactions (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- ubiquitination, ubiquitin chains, post-translational modification, protein phosphorylation, proteasomal degradation, allosteric regulation
- MeSH terms
- Humans, Lysine, Models, Molecular, Phosphorylation, Protein Processing, Post-Translational, Signal Transduction, Protein Structure, Tertiary, Ubiquitin, Proteasome Endopeptidase Complex, Ubiquitination
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