ArticleThe Journal of clinical investigation2018
Inadequate ubiquitination-proteasome coupling contributes to myocardial ischemia-reperfusion injury.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Coenzyme QFrontiers in cardiovascular medicine · 2022Pooled it
- The ubiquitin system in heart and vessel pathobiology: From mechanisms to therapeutic strategies.Genes & diseases · 2026Review
- Review
- Ubiquitin-Related Proteostatic Programs in Cycling Fibroblast-Lineage Remodeling After Myocardial Ischemic Injury: A Hypothesis Informed by Single-Cell and Spatial Transcriptomics.International journal of molecular sciences · 2026Review
- TRIM28 Is an E3 Ligase of IRP2 Suppressing Ischemia/Reperfusion-Induced Myocardial Ferroptosis.Circulation · 2026Article
- Ubiquitin-specific protease 25: a new regulator for cardiovascular and cerebrovascular diseases.Frontiers in cell and developmental biology · 2026Review
- The role of ubiquitination in the pathogenesis of atrial fibrillation: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- The E3 ubiquitin ligase MARCH2 protects against myocardial ischemia-reperfusion injury through inhibiting pyroptosis via negative regulation of PGAM5/MAVS/NLRP3 axis.Cell discovery · 2024Article
- Shaping cardiac destiny: the role of post-translational modifications on endoplasmic reticulum - mitochondria crosstalk in cardiac remodeling.Frontiers in pharmacology · 2024Review
- Protein homeostasis in the aged and diseased heart.The journal of cardiovascular aging · 2023Article
- Impact of Cardiovascular Diseases on Ischemic Stroke Outcomes.Journal of integrative neuroscience · 2022Review
- Role of sevoflurane in myocardial ischemia-reperfusion injury via the ubiquitin-specific protease 22/lysine-specific demethylase 3A axis.Bioengineered · 2022Article
- Acetylcholine exerts cytoprotection against hypoxia/reoxygenation-induced apoptosis, autophagy and mitochondrial impairment through both muscarinic and nicotinic receptors.Apoptosis : an international journal on programmed cell death · 2022Article
- Fibronectin type III domain-containing 5 improves aging-related cardiac dysfunction in mice.Aging cell · 2022Article
- Osteocrin, a novel myokine, prevents diabetic cardiomyopathy via restoring proteasomal activity.Cell death & disease · 2021Article
- Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis.Frontiers in endocrinology · 2021Article
- CHIP phosphorylation by protein kinase G enhances protein quality control and attenuates cardiac ischemic injury.Nature communications · 2020Article
- The impacts of ubiquilin 1 (UBQLN1) knockdown on cells viability, proliferation, and apoptosis are mediated by p53 in A549 lung cancer cells.Journal of thoracic disease · 2020Article
- Crosstalk between cardiomyocytes and noncardiomyocytes is essential to prevent cardiomyocyte apoptosis induced by proteasome inhibition.Cell death & disease · 2020Article
Corrections and comments
- Commented on by
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The ubiquitin-proteasome system (UPS) degrades a protein molecule via 2 main steps: ubiquitination and proteasomal degradation. Extraproteasomal ubiquitin receptors are thought to couple the 2 steps, but this proposition has not been tested in vivo with vertebrates. More importantly, impaired UPS performance plays a major role in cardiac pathogenesis, including myocardial ischemia-reperfusion injury (IRI), but the molecular basis of UPS impairment remains poorly understood. Ubiquilin1 is a bona fide extraproteasomal ubiquitin receptor. Here, we report that mice with a cardiomyocyte-restricted knockout of Ubiquilin1 (Ubqln1-CKO mice) accumulated a surrogate UPS substrate (GFPdgn) and increased myocardial ubiquitinated proteins without altering proteasome activities, resulting in late-onset cardiomyopathy and a markedly shortened life span. When subject to regional myocardial ischemia-reperfusion, young Ubqln1-CKO mice showed substantially exacerbated cardiac malfunction and enlarged infarct size, and conversely, mice with transgenic Ubqln1 overexpression displayed attenuated IRI. Furthermore, Ubqln1 overexpression facilitated proteasomal degradation of oxidized proteins and the degradation of a UPS surrogate substrate in cultured cardiomyocytes without increasing autophagic flux. These findings demonstrate that Ubiquilin1 is essential to cardiac ubiquitination-proteasome coupling and that an inadequacy in the coupling represents a major pathogenic factor for myocardial IRI; therefore, strategies to strengthen coupling have the potential to reduce IRI.
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.