ArticlePloS one2018
The N-recognin UBR4 of the N-end rule pathway is required for neurogenesis and homeostasis of cell surface proteins.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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
24 citing papers in PubMed, 39 citations in OpenAlex.
- Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026Review
- Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.Nature communications · 2026Article
- Turnover of missense mutant cytosolic proteins proceeds in the absence of major quality control E3 ligases.microPublication biology · 2026Article
- A pathogenic variant of AMOT leads to isolated X-linked congenital hydrocephalus due to N-terminal truncation.The Journal of clinical investigation · 2025Article
- Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.Science (New York, N.Y.) · 2025Article
- Tumor-promoting UBR4 coordinates impaired mitophagy-associated senescence and lung adenocarcinoma pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TRIM52 maintains cellular fitness and is under tight proteolytic control by multiple giant E3 ligases.Nature communications · 2025Article
- Integrative gene regulatory network analysis discloses key driver genes of fibromuscular dysplasia.Nature cardiovascular research · 2024Article
- Insights into the recognition mechanism in the UBR box of UBR4 for its specific substrates.Communications biology · 2023Article
- P65 mediated UBR4 in exosomes derived from menstrual blood stromal cells to reduce endometrial fibrosis by regulating YAP Ubiquitination.Journal of nanobiotechnology · 2023Article
- Article
- Case report: Episodic ataxia without ataxia?Frontiers in neurology · 2023Article
- UBR4/POE facilitates secretory trafficking to maintain circadian clock synchrony.Nature communications · 2022Article
- Human papillomavirus E6 and E7: What remains?Tumour virus research · 2021Review
- NOX5 is expressed aberrantly but not a critical pathogenetic gene in Hirschsprung disease.BMC pediatrics · 2021Article
- Antagonistic control of myofiber size and muscle protein quality control by the ubiquitin ligase UBR4 during aging.Nature communications · 2021Article
- It's not just a phase; ubiquitination in cytosolic protein quality control.Biochemical Society transactions · 2021Review
- The ATF3 Transcription Factor Is a Short-Lived Substrate of the Arg/N-Degron Pathway.Biochemistry · 2020Article
- Recognition of nonproline N-terminal residues by the Pro/N-degron pathway.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Five enzymes of the Arg/N-degron pathway form a targeting complex: The concept of superchanneling.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The N-end rule pathway is a proteolytic system in which single N-terminal amino acids of proteins act as a class of degrons (N-degrons) that determine the half-lives of proteins. We have previously identified a family of mammals N-recognins (termed UBR1, UBR2, UBR4/p600, and UBR5/EDD) whose conserved UBR boxes bind N-degrons to facilitate substrate ubiquitination and proteasomal degradation via the ubiquitin-proteasome system (UPS). Amongst these N-recognins, UBR1 and UBR2 mediate ubiquitination and proteolysis of short-lived regulators and misfolded proteins. Here, we characterized the null phenotypes of UBR4-deficient mice in which the UBR box of UBR4 was deleted. We show that the mutant mice die around embryonic days 9.5-10.5 (E9.5-E10.5) associated with abnormalities in various developmental processes such as neurogenesis and cardiovascular development. These developmental defects are significantly attributed to the inability to maintain cell integrity and adhesion, which significantly correlates to the severity of null phenotypes. UBR4-loss induces the depletion of many, but not all, proteins from the plasma membrane, suggesting that UBR4 is involved in proteome-wide turnover of cell surface proteins. Indeed, UBR4 is associated with and required to generate the multivesicular body (MVB) which transiently store endocytosed cell surface proteins before their targeting to autophagosomes and subsequently lysosomes. Our results suggest that the N-recognin UBR4 plays a role in the homeostasis of cell surface proteins and, thus, cell adhesion and integrity.
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.