The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
UBQLN2 Mediates Autophagy-Independent Protein Aggregate Clearance by the Proteasome
Open accessAbstract
Clearance of misfolded and aggregated proteins is central to cell survival. Here, we describe a new pathway for maintaining protein homeostasis mediated by the proteasome shuttle factor UBQLN2. The 26S proteasome degrades polyubiquitylated substrates by recognizing them through stoichiometrically bound ubiquitin receptors, but substrates are also delivered by reversibly bound shuttles. We aimed to determine why these parallel delivery mechanisms exist and found that UBQLN2 acts with the HSP70-HSP110 disaggregase machinery to clear protein aggregates via the 26S proteasome. UBQLN2 recognizes client-bound HSP70 and links it to the proteasome to allow for the degradation of aggregated and misfolded proteins. We further show that this process is active in the cell nucleus, where another system for aggregate clearance, autophagy, does not act. Finally, we found that mutations in UBQLN2, which lead to neurodegeneration in humans, are defective in chaperone binding, impair aggregate clearance, and cause cognitive deficits in mice.
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Cites
The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction
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Self-citationTowards a proteome-scale map of the human protein–protein interaction network
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Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia
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Cited by
Molecular definitions of autophagy and related processes
Galluzzi, L., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cecconi, F., Choi, A. M., Chu, C. T., Codogno, P., Colombo, M. I., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796697 · Cited by 1,646
The glymphatic pathway in neurological disorders.
Rasmussen, M. K., Mestre, H., & Nedergaard, M. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30318-1 · Cited by 1,560
Ubiquitin ligases in oncogenic transformation and cancer therapy
Senft, D., Qi, J., & Ronai, Z. A. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.105 · Cited by 489
Cellular Handling of Protein Aggregates by Disaggregation Machines
Mogk, A., Bukau, B., & Kampinga, H. H. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.01.004 · Cited by 365
Selective autophagy as a potential therapeutic target for neurodegenerative disorders
Scrivo, A., Bourdenx, M., Pampliega, O., & Cuervo, A. M. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30238-2 · Cited by 355
Metadata
- Authors
- Hjerpe, R., Bett, J. S., Keuss, M. J., Solovyova, A., McWilliams, T. G., Johnson, C., Sahu, I., Varghese, J., Wood, N., Wightman, M., Osborne, G., Bates, G. P., Glickman, M. H., Trost, M., Knebel, A., Marchesi, F., & Kurz, T.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 166
- Issue
- 4
- Pages
- 935-949
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2497525607
- Cited by
- 309
- References
- 42
- FWCI
- 17.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Hjerpe, R., Bett, J. S., Keuss, M. J., Solovyova, A., McWilliams, T. G., Johnson, C., Sahu, I., Varghese, J., Wood, N., Wightman, M., Osborne, G., Bates, G. P., Glickman, M. H., Trost, M., Knebel, A., Marchesi, F., & Kurz, T. (2016). UBQLN2 Mediates Autophagy-Independent Protein Aggregate Clearance by the Proteasome. Cell. https://doi.org/10.1016/j.cell.2016.07.001
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
