Recognition and Processing of Ubiquitin-Protein Conjugates by the Proteasome
Open accessAbstract
The proteasome is an intricate molecular machine, which serves to degrade proteins following their conjugation to ubiquitin. Substrates dock onto the proteasome at its 19-subunit regulatory particle via a diverse set of ubiquitin receptors and are then translocated into an internal chamber within the 28-subunit proteolytic core particle (CP), where they are hydrolyzed. Substrate is threaded into the CP through a narrow gated channel, and thus translocation requires unfolding of the substrate. Six distinct ATPases in the regulatory particle appear to form a ring complex and to drive unfolding as well as translocation. ATP-dependent, degradation-coupled deubiquitination of the substrate is required both for efficient substrate degradation and for preventing the degradation of the ubiquitin tag. However, the proteasome also contains deubiquitinating enzymes (DUBs) that can remove ubiquitin before substrate degradation initiates, thus allowing some substrates to dissociate from the proteasome and escape degradation. Here we examine the key elements of this molecular machine and how they cooperate in the processing of proteolytic substrates.
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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 [7]
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 [7]
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- Authors
- Finley, D.
- Affiliations
- Harvard University (US)
- Corresponding author
- Finley, Daniel
- ORCID
- Finley, Daniel
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2009-06-01
- Volume
- 78
- Issue
- 1
- Pages
- 477-513
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- PMC
- PMC3431160
- OpenAlex
- W2097164847
- Cited by
- 1,764
- References
- 4
- Citations by year
- 2026: 55 · 2025: 74 · 2024: 86 · 2023: 97 · 2022: 96 · 2021: 96 · 2020: 110 · 2019: 96 · 2018: 100 · 2017: 94 · 2016: 110 · 2015: 111 · 2014: 134 · 2013: 129 · 2012: 145
- FWCI
- 9.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM043601, GM43601, R01GM065592, GM065592, R37GM043601)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 082906, R21DK082906)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- proteasome, ubiquitin conjugates, protein degradation, ubiquitin receptors, ATPase, substrate unfolding, substrate translocation, deubiquitination, deubiquitinase
- MeSH terms
- Animals, Humans, Proteins, Arabidopsis, Ubiquitin, Proteasome Endopeptidase Complex
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