ArticleThe Journal of cell biology2020
UBR E3 ligases and the PDIA3 protease control degradation of unfolded antibody heavy chain by ERAD.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Pooled it
- Proteasome Inhibition Amplifies Endoplasmic Reticulum (ER) Stress Responses: Comparative Proteomics of Chinese Hamster Ovary Cell Lines.Biomolecules · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Proteomic and Ubiquitinated Proteome Insights Into ER Stress Responses in Chinese Hamster Ovary Cells Under Mild Hypothermic Conditions.Biotechnology and bioengineering · 2026Article
- Recent Advances in Engineering the Unfolded Protein Response in Recombinant Chinese Hamster Ovary Cell Lines.International journal of molecular sciences · 2025Review
- Characterization of the Ubiquitin-Modified Proteome of Recombinant Chinese Hamster Ovary Cells in Response to Endoplasmic Reticulum Stress.Biotechnology journal · 2024Article
- BIG enhances Arg/N-degron pathway-mediated protein degradation to regulate Arabidopsis hypoxia responses and suberin deposition.The Plant cell · 2024Article
- NAP1L1 regulates BIRC2 ubiquitination modification via E3 ubiquitin ligase UBR4 and hence determines hepatocellular carcinoma progression.Cell death discovery · 2024Article
- Insights into the recognition mechanism in the UBR box of UBR4 for its specific substrates.Communications biology · 2023Article
- PDIA3 Expression Is Altered in the Limbic Brain Regions of Triple-Transgenic Mouse Model of Alzheimer's Disease.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of unfolded antibody chains in the ER triggers ER stress that may lead to reduced productivity in therapeutic antibody manufacturing processes. We identified UBR4 and UBR5 as ubiquitin E3 ligases involved in HC ER-associated degradation. Knockdown of UBR4 and UBR5 resulted in intracellular accumulation, enhanced secretion, and reduced ubiquitination of HC. In concert with these E3 ligases, PDIA3 was shown to cleave ubiquitinated HC molecules to accelerate HC dislocation. Interestingly, UBR5, and to a lesser degree UBR4, were down-regulated as cellular demand for antibody expression increased in CHO cells during the production phase, or in plasma B cells. Reducing UBR4/UBR5 expression before the production phase increased antibody productivity in CHO cells, possibly by redirecting antibody molecules from degradation to secretion. Altogether we have characterized a novel proteolysis/proteasome-dependent pathway involved in degradation of unfolded antibody HC. Proteins characterized in this pathway may be novel targets for CHO cell engineering.
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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.