ArticleMolecular cell2020
DDI2 Is a Ubiquitin-Directed Endoprotease Responsible for Cleavage of Transcription Factor NRF1.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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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
51 citing papers in PubMed, 85 citations in OpenAlex.
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- Nrf3: an emerging player in cancer, inflammation, and cellular homeostasis.Molecular biology reports · 2026Review
- K48-ubiquitin-dependent proteases cut-up post-ER proteins.Nature communications · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Urinary Proteomic Signatures in Sickle Cell Disease: Search for Biomarkers Associated With Underlying Molecular Pathways.Advances in hematology · 2026Article
- Isotope Dilution nanoLC-MS/MS Quantitation of Methylglyoxal DNA-Protein Crosslinks: Formation and Repair in Human Cells.bioRxiv : the preprint server for biology · 2025Article
- The HCV-Dependent Inhibition of Nrf1/ARE-Mediated Gene Expression Favours Viral Morphogenesis.Viruses · 2025Article
- Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2.PLoS genetics · 2025Article
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- NF-E2-related factor 1 suppresses the expression of a spermine oxidase and the production of highly reactive acrolein.Scientific reports · 2025Article
- Stress responses induced by perturbation of the ubiquitin-proteasome system.Trends in biochemical sciences · 2025Review
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.Science advances · 2025Article
- Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories.Cell stress · 2025Review
- SPRTN metalloprotease participates in repair of ROS-mediated DNA-protein crosslinks.Scientific reports · 2024Article
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- PARP1-dependent DNA-protein crosslink repair.Nature communications · 2024Article
- Ferroptosis regulation by Cap'n'collar family transcription factors.The Journal of biological chemistry · 2024Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
The Ddi1/DDI2 proteins are ubiquitin shuttling factors, implicated in a variety of cellular functions. In addition to ubiquitin-binding and ubiquitin-like domains, they contain a conserved region with similarity to retroviral proteases, but whether and how DDI2 functions as a protease has remained unknown. Here, we show that DDI2 knockout cells are sensitive to proteasome inhibition and accumulate high-molecular weight, ubiquitylated proteins that are poorly degraded by the proteasome. These proteins are targets for the protease activity of purified DDI2. No evidence for DDI2 acting as a de-ubiquitylating enzyme was uncovered, which could suggest that it cleaves the ubiquitylated protein itself. In support of this idea, cleavage of transcription factor NRF1 is known to require DDI2 activity in vivo. We show that DDI2 is indeed capable of cleaving NRF1 in vitro but only when NRF1 protein is highly poly-ubiquitylated. Together, these data suggest that DDI2 is a ubiquitin-directed endoprotease.
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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.