ArticleThe Journal of biological chemistry2005
Lys6-modified ubiquitin inhibits ubiquitin-dependent protein degradation.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 86 citations in OpenAlex.
- Post-translational modifications as a regulatory code for tau function in health and disease.Frontiers in dementia · 2026Review
- Ubiquitin signatures on aggregating proteins in neurodegeneration.Essays in biochemistry · 2025Review
- Glycative stress as a cause of macular degeneration.Progress in retinal and eye research · 2024Review
- Unbalanced redox status network as an early pathological event in congenital cataracts.Redox biology · 2023Article
- Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022Review
- Functional roles of E3 ubiquitin ligases in prostate cancer.Journal of molecular medicine (Berlin, Germany) · 2022Review
- RNF6 as an Oncogene and Potential Therapeutic Target-A Review.Biotech (Basel (Switzerland)) · 2020Review
- A ubiquitin variant-based affinity approach selectively identifies substrates of the ubiquitin ligase E6AP in complex with HPV-11 E6 or HPV-16 E6.The Journal of biological chemistry · 2020Article
- The diversity of linkage-specific polyubiquitin chains and their role in synaptic plasticity and memory formation.Neurobiology of learning and memory · 2020Review
- Direct regulation of Chk1 protein stability by E3 ubiquitin ligase HUWE1.The FEBS journal · 2020Article
- Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications.Cellular and molecular life sciences : CMLS · 2020Review
- Stabilization of p27FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Concise machinery for monitoring ubiquitination activities using novel artificial RING fingers.Protein science : a publication of the Protein Society · 2018Review
- Disassembly of the lens fiber cell nucleus to create a clear lens: The p27 descent.Experimental eye research · 2017Review
- Age-related changes in the proteostasis network in the brain of the naked mole-rat: Implications promoting healthy longevity.Biochimica et biophysica acta · 2015Article
- Substrate degradation by the proteasome: a single-molecule kinetic analysis.Science (New York, N.Y.) · 2015Article
- Altered ubiquitin causes perturbed calcium homeostasis, hyperactivation of calpain, dysregulated differentiation, and cataract.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin.The EMBO journal · 2014Article
- Newborn mouse lens proteome and its alteration by lysine 6 mutant ubiquitin.Journal of proteome research · 2014Article
- Chemical strategies to understand the language of ubiquitin signaling.Biopolymers · 2014Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Ubiquitin plays essential roles in various cellular processes; therefore, it is of keen interest to study the structure-function relationship of ubiquitin itself. We investigated the modification of Lys(6) of ubiquitin and its physiological consequences. Mass spectrometry-based peptide mapping and N-terminal sequencing demonstrated that, of the 7 Lys residues in ubiquitin, Lys(6) was the most readily labeled with sulfosuccinimidobiotin. Lys(6)-biotinylated ubiquitin was incorporated into high molecular mass ubiquitin conjugates as efficiently as unmodified ubiquitin. However, Lys(6)-biotinylated ubiquitin inhibited ubiquitin-dependent proteolysis, as conjugates formed with Lys(6)-biotinylated ubiquitin were resistant to proteasomal degradation. Ubiquitins with a mutation of Lys(6) had similar phenotypes as Lys(6)-biotinylated ubiquitin. Lys(6) mutant ubiquitins (K6A, K6R, and K6W) also inhibited ATP-dependent proteolysis and caused accumulation of ubiquitin conjugates. Conjugates formed with K6W mutant ubiquitin were also resistant to proteasomal degradation. The dominant-negative effect of Lys(6)-modified ubiquitin was further demonstrated in intact cells. Overexpression of K6W mutant ubiquitin resulted in accumulation of intracellular ubiquitin conjugates, stabilization of typical substrates for ubiquitin-dependent proteolysis, and enhanced susceptibility to oxidative stress. Taken together, these results show that Lys(6)-modified ubiquitin is a potent and specific inhibitor of ubiquitin-mediated protein degradation.
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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.