Identification of a quality-control factor that monitors failures during proteasome assembly
Open accessAbstract
Safeguarding protein complex assembly: The assembly of multiprotein complexes inside the cell requires each subunit to be produced at a defined level relative to its partners. Imbalances in subunit synthesis are inevitable, necessitating the elimination of unassembled intermediates. Zavodszky et al . found that a ubiquitin ligase called HERC1 is responsible for marking certain assembly intermediates of the proteasome for degradation. HERC1 finds these intermediates by recognizing a proteasome assembly factor that normally dissociates when assembly is complete. A point mutation in HERC1 that impairs its ability to recognize proteasome assembly intermediates causes neurodegeneration in mice, highlighting the importance of this quality control pathway. —SMH
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iPSCs and germ layer cells may compensate for the detrimental effects of PSMC5 variant p.(Arg325Trp) by monoallelic expression of the wild-type PSMC5 allele and/or an enhanced capacity to selectively eliminate defective proteasome assembly intermediates.
“this observation suggests that iPSCs and germ layer cells may compensate for the detrimental effects of PSMC5 variant p.(Arg325Trp) by monoallelic expression of the wild-type PSMC5 allele and/or an enhanced capacity to selectively eliminate defective proteasome assembly intermediates27.”
From Investigating the neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies (2025) · cites this paper as [27]
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Experimental — accuracy not yet measuredPSMC5 that is not incorporated into proteasomes is unstable.
“Since the PSMC5 that is not incorporated into proteasomes will be unstable [33]”
From PSMC5 insufficiency and P320R mutation impair proteasome function (2024) · cites this paper as [33]
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- Authors
- Zavodszky, E., Peak-Chew, S.-Y., Juszkiewicz, S., Narvaez, A. J., & Hegde, R. S.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- MRC Laboratory of Molecular Biology, Cambridge, UK.
- AstraZeneca (United Kingdom) (GB)
- Corresponding author
- Hegde, Ramanujan S.
- Venue
- Science
- Published
- 2021-08-27
- Volume
- 373
- Issue
- 6558
- Pages
- 998-1004
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7611656
- OpenAlex
- W3195624899
- Cited by
- 45
- References
- 52
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 8 · 2023: 9 · 2022: 12 · 2021: 2
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Medical Research Council (MC_ UP_A022_1007)
- LMB-AZ BlueSky Fund (BSF27)
- 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
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- proteasome assembly, protein quality control, protein degradation, assembly intermediates, ubiquitination, neurodegeneration, proteostasis, multiprotein complex assembly
- MeSH terms
- ATPases Associated with Diverse Cellular Activities, Animals, Calmodulin, Humans, Mutation, Proto-Oncogene Proteins, Point Mutation, Neurodegenerative Diseases, Mutation, Missense, Protein Subunits, Ubiquitin-Protein Ligases, Proteasome Endopeptidase Complex, Adaptor Proteins, Signal Transducing, Mice, Protein Interaction Domains and Motifs, Ubiquitination, Proteolysis, MCF-7 Cells
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