ArticleProceedings of the National Academy of Sciences of the United States of America2015
Altered ubiquitin causes perturbed calcium homeostasis, hyperactivation of calpain, dysregulated differentiation, and cataract.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract.Communications biology · 2020Pooled it
- Thyroid hormone signaling in ocular development and diseases.Biological research · 2025Review
- TGF-β1-induced m6A modifications accelerate onset of nuclear cataract in high myopia by modulating the PCP pathway.Nature communications · 2025Article
- Research Progress on the Role of Ubiquitination in Eye Diseases.Cell biochemistry and biophysics · 2024Review
- Smurf1 Modulates Smad Signaling Pathway in Fibrotic Cataract Formation.Investigative ophthalmology & visual science · 2024Article
- N6-methyladenosine methylation in ophthalmic diseases: From mechanisms to potential applications.Heliyon · 2024Review
- Inhibitory effect of Nifedipine on aldose reductase delays cataract progression.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Unbalanced redox status network as an early pathological event in congenital cataracts.Redox biology · 2023Article
- Identification and quantification of ionising radiation-induced oxysterol formation in membranes of lens fibre cells.Advances in redox research · 2023Article
- Calpain activity is negatively regulated by a KCTD7-Cullin-3 complex via non-degradative ubiquitination.Cell discovery · 2023Article
- Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022Review
- Article
- Genome-wide association study reveals the genetic architecture for calcium accumulation in grains of hexaploid wheat (Triticum aestivum L.).BMC plant biology · 2022Article
- The E3 Ligase RNF157 Inhibits Lens Epithelial Cell Apoptosis by Negatively Regulating p53 in Age-Related Cataracts.Investigative ophthalmology & visual science · 2022Article
- Connexin Mutants Cause Cataracts Through Deposition of Apatite.Frontiers in cell and developmental biology · 2022Article
- Loss of fiber cell communication may contribute to the development of cataracts of many different etiologies.Frontiers in physiology · 2022Review
- Mutations of CX46/CX50 and Cataract Development.Frontiers in molecular biosciences · 2022Review
- RNA-binding proteins and post-transcriptional regulation in lens biology and cataract: Mediating spatiotemporal expression of key factors that control the cell cycle, transcription, cytoskeleton and transparency.Experimental eye research · 2022Review
- Molecular mechanisms underlying enhanced hemichannel function of a cataract-associated Cx50 mutant.Biophysical journal · 2021Article
- Aged Nrf2-Null Mice Develop All Major Types of Age-Related Cataracts.Investigative ophthalmology & visual science · 2021Article
Corrections and comments
- Erratum issuedCorrection for Liu et al., Altered ubiquitin causes perturbed calcium homeostasis, hyperactivation of calpain, dysregulated differentiation, and cataract.2015 · Jian, Shuhong [corrected to Jiang, Shuhong]
Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
Abstract
Although the ocular lens shares many features with other tissues, it is unique in that it retains its cells throughout life, making it ideal for studies of differentiation/development. Precipitation of proteins results in lens opacification, or cataract, the major blinding disease. Lysines on ubiquitin (Ub) determine fates of Ub-protein substrates. Information regarding ubiquitin proteasome systems (UPSs), specifically of K6 in ubiquitin, is undeveloped. We expressed in the lens a mutant Ub containing a K6W substitution (K6W-Ub). Protein profiles of lenses that express wild-type ubiquitin (WT-Ub) or K6W-Ub differ by only ∼2%. Despite these quantitatively minor differences, in K6W-Ub lenses and multiple model systems we observed a fourfold Ca(2+) elevation and hyperactivation of calpain in the core of the lens, as well as calpain-associated fragmentation of critical lens proteins including Filensin, Fodrin, Vimentin, β-Crystallin, Caprin family member 2, and tudor domain containing 7. Truncations can be cataractogenic. Additionally, we observed accumulation of gap junction Connexin43, and diminished Connexin46 levels in vivo and in vitro. These findings suggest that mutation of Ub K6 alters UPS function, perturbs gap junction function, resulting in Ca(2+) elevation, hyperactivation of calpain, and associated cleavage of substrates, culminating in developmental defects and a cataractous lens. The data show previously unidentified connections between UPS and calpain-based degradative systems and advance our understanding of roles for Ub K6 in eye development. They also inform about new approaches to delay cataract and other protein precipitation diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.