ArticleInvestigative ophthalmology & visual science2010
Ubiquitin proteasome pathway-mediated degradation of proteins: effects due to site-specific substrate deamidation.
Article in Investigative ophthalmology & visual science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Expanding the Chemoproteomic Toolkit to Asparagine and Glutamine.ACS chemical biology · 2026Article
- Sex-specific effects of acetylation on tauopathy in aging htau mice.Scientific reports · 2026Article
- Chronic Alcohol Consumption Reprograms Hepatic Metabolism Through Organelle-Specific Acetylation in Mice.Molecular & cellular proteomics : MCP · 2025Article
- Reversible cold-induced lens opacity in a hibernator reveals a molecular target for treating cataracts.The Journal of clinical investigation · 2024Article
- Smurf1 Modulates Smad Signaling Pathway in Fibrotic Cataract Formation.Investigative ophthalmology & visual science · 2024Article
- Nonenzymatic Posttranslational Modifications and Peptide Cleavages Observed in Peptide Epimers.Journal of the American Society for Mass Spectrometry · 2023Article
- Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022Review
- Mechanisms of Deamidation of Asparagine Residues and Effects of Main-Chain Conformation on Activation Energy.International journal of molecular sciences · 2020Article
- Polyubiquitin Chains Linked by Lysine Residue 48 (K48) Selectively Target Oxidized ProteinsAntioxidants & redox signaling · 2019Article
- Computational Studies on the Nonenzymatic Deamidation Mechanisms of Glutamine Residues.ACS omega · 2019Article
- Hepatic Mitochondrial Defects in a Nonalcoholic Fatty Liver Disease Mouse Model Are Associated with Increased Degradation of Oxidative Phosphorylation Subunits.Molecular & cellular proteomics : MCP · 2018Article
- Investigation of Novel Regulation of N-myristoyltransferase by Mammalian Target of Rapamycin in Breast Cancer Cells.Scientific reports · 2018Article
- Expression Profiling of DNA Methylation and Transcriptional Repression Associated Genes in Lens Epithelium Cells of Age-Related Cataract.Cellular and molecular neurobiology · 2017Article
- Release of skeletal muscle peptide fragments identifies individual proteins degraded during insulin deprivation in type 1 diabetic humans and mice.American journal of physiology. Endocrinology and metabolism · 2016Article
- Gender differences in white matter pathology and mitochondrial dysfunction in Alzheimer's disease with cerebrovascular disease.Molecular brain · 2016Article
- Article
- Common cell biologic and biochemical changes in aging and age-related diseases of the eye: toward new therapeutic approaches to age-related ocular diseases.Investigative ophthalmology & visual science · 2013Review
- Enhancement of ubiquitin conjugation activity reduces intracellular aggregation of V76D mutant γD-crystallin.Investigative ophthalmology & visual science · 2012Article
- Roles for the ubiquitin-proteasome pathway in protein quality control and signaling in the retina: implications in the pathogenesis of age-related macular degeneration.Molecular aspects of medicine · 2012Review
- Oligomerization with wt αA- and αB-crystallins reduces proteasome-mediated degradation of C-terminally truncated αA-crystallin.Investigative ophthalmology & visual science · 2012Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
purposeThe accumulation, aggregation, and precipitation of proteins is etiologic for age-related diseases, particularly cataract, because the precipitates cloud the lens. Deamidation of crystallins is associated with protein precipitation, aging, and cataract. Among the roles of the ubiquitin proteasome pathway (UPP) is protein surveillance and maintenance of protein quality. The purpose of this study was to determine whether deamidation can alter clearance of crystallins by the UPP.
methodsWild-type (WT) and deamidated crystallins were expressed and (125)I-radiolabeled. Ubiquitination and degradation were monitored separately.
resultsFor betaB2 crystallins, rates of ubiquitination and adenosine triphosphate-dependent degradation, both indicators of active UPP, occurred in the order Q70E/Q162E>Q162E> Q70E=WT betaB2 using reticulocyte lysate as the source of degradation machinery. Human lens epithelial cell lysates and lens fiber cell lysates also catalyzed ubiquitination but only limited degradation. Supplementation with proteasome failed to enhance degradation. Rates of ubiquitination and degradation of WT and deamidated betaB1 crystallins were rapid and showed little relationship to the site of deamidation using N157D and Q204E mutants. gammaD-Crystallins were not degraded by the UPP. Deamidation altered amine reactivity, circular dichroism spectra, surface hydrophobicity, and thermal stability.
conclusionsThese data demonstrate for the first time that, like mild oxidative stress, deamidation of some proteins makes them preferred substrates for ubiquitination and, in some cells, for UPP-dependent degradation. Failure to properly execute ubiquitination and degrade the ubiquitin-conjugates may explain their accumulation on aging and in cataractogenesis.
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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.