ArticleNature chemical biology2014
Extended ubiquitin species are protein-based DUB inhibitors.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- ZOMES: expanding roles of the PCI complexes from protein metabolism to drug discovery.npj metabolic health and disease · 2026Article
- Molecular mechanisms underlying p62-dependent secretion of the Alzheimer-associated ubiquitin variant UBBProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Altered ubiquitin signaling induces Alzheimer's disease-like hallmarks in a three-dimensional human neural cell culture model.Nature communications · 2023Article
- Strategies for Monitoring "Ubiquitin C-Terminal Hydrolase 1" (Yuh1) Activity.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Ubiquitin and Ubiquitin-like Proteins in Cancer, Neurodegenerative Disorders, and Heart Diseases.International journal of molecular sciences · 2022Review
- The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag.Nature communications · 2021Article
- Review
- The Dose-Dependent Pleiotropic Effects of the UBBFrontiers in molecular biosciences · 2021Review
- Recent Insights on Alzheimer's Disease Originating from Yeast Models.International journal of molecular sciences · 2018Review
- Different Expression Levels of Human Mutant Ubiquitin BFrontiers in molecular neuroscience · 2018Article
- Dysfunction of Protein Quality Control in Parkinsonism-Dementia Complex of Guam.Frontiers in neurology · 2018Article
- Selective Transgenic Expression of Mutant Ubiquitin in Purkinje Cell Stripes in the Cerebellum.Cerebellum (London, England) · 2017Article
- Commentary: The landscape of transcription errors in eukaryotic cells.Frontiers in genetics · 2017Article
- Characterizing polyubiquitinated forms of the neurodegenerative ubiquitin mutant UBBFEBS letters · 2016Article
- Accumulation of Basic Amino Acids at Mitochondria Dictates the Cytotoxicity of Aberrant Ubiquitin.Cell reports · 2015Article
- Disassembly of Lys11 and mixed linkage polyubiquitin conjugates provides insights into function of proteasomal deubiquitinases Rpn11 and Ubp6.The Journal of biological chemistry · 2015Article
- Misframed ubiquitin and impaired protein quality control: an early event in Alzheimer's disease.Frontiers in molecular neuroscience · 2015Review
- Localization of mutant ubiquitin in the brain of a transgenic mouse line with proteasomal inhibition and its validation at specific sites in Alzheimer's disease.Frontiers in neuroanatomy · 2015Article
- Ubiquitin-dependent proteolysis in yeast cells expressing neurotoxic proteins.Frontiers in molecular neuroscience · 2015Review
- Spermidine protects against α-synuclein neurotoxicity.Cell cycle (Georgetown, Tex.) · 2014Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
A frameshift mutation in the transcript of the ubiquitin-B gene leads to a C-terminally extended ubiquitin (Ub), UBB(+1). UBB(+1) has been considered to inhibit proteasomes and as such to be the underlying cause for toxic protein buildup correlated with certain neuropathological conditions. We demonstrate that expression of extended Ub variants leads to accumulation of heterogeneously linked polyubiquitin conjugates, indicating a pervasive effect on Ub-dependent turnover. 20S proteasomes selectively proteolyzed Ub extensions, yet no evidence for inhibition of 26S holoenzymes was found. However, among susceptible targets for inhibition was Ubp6, the primary enzyme responsible for disassembly of Lys48 linkages at 26S proteasomes. Processing of Lys48 and Lys63 linkages by other deubiquitinating enzymes (DUBs) was also inhibited. Disruption of Ub-dependent degradation by extended Ub variants may therefore be attributed to their inhibitory effect on select DUBs, thus shifting research efforts related to protein accumulation in neurodegenerative processes from proteasomes to DUBs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.