ArticleCell2014
Key steps in ERAD of luminal ER proteins reconstituted with purified components.
Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
What it found
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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
131 citing papers in PubMed, 211 citations in OpenAlex.
- FAF1 and FAF2 enhance unfolding by p97-UFD1-NPL4 complex enabling rational design of p97 activators.The EMBO journal · 2026Article
- FAF1 cofactor enhances UFD1/NPL4-p97 unfolding efficiency across ubiquitin chain lengths independent of SUMO2.bioRxiv : the preprint server for biology · 2026Article
- Comparative analysis of Cdc48-dependent proteolysis at the ER, mitochondria and chloroplasts.Nature communications · 2026Review
- Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement.Cell reports · 2026Article
- Direct observation of ATP-driven ubiquitin chain handling by Cdc48.Nature communications · 2026Article
- SEL1L3 suppresses colorectal cancer cell growth and metastasis by preventing endoplasmic reticulum-associated degradation of STING.Cell death & disease · 2026Article
- The deubiquitinating enzyme Otu1 releases substrates from the conserved initiation complex of the Cdc48/p97 ATPase for proteasomal degradation.Scientific reports · 2026Article
- O-mannosylation of misfolded ER proteins promotes ERAD.The EMBO journal · 2026Article
- NPLOC4 Inhibition Remodels Tumor Microenvironment via M2-to-M1 Macrophage Reprogramming and Boosts Anti-PD-1 Response in Liver Cancer.International journal of biological sciences · 2026Article
- Competition between Der1 and ERAD-M substrates controls Hrd1 complex function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A UBH-UBX module amplifies p97/VCP's unfolding power to facilitate protein extraction and degradation.Nature communications · 2025Article
- The deubiquitinating enzyme Otu1 releases substrates from the conserved initiation complex of the Cdc48/p97 ATPase for proteasomal degradation.bioRxiv : the preprint server for biology · 2025Article
- Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement.bioRxiv : the preprint server for biology · 2025Article
- UBE2J2 sensitizes the ERAD ubiquitination cascade to changes in membrane lipid saturation.Nature communications · 2025Article
- Hydroxyurea modulates thiol-disulfide homeostasis in the yeast endoplasmic reticulum.Life science alliance · 2025Article
- SEL1L-HRD1-mediated ERAD in mammals.Nature cell biology · 2025Review
- The Erv41-Erv46 complex serves as a retrograde receptor to retrieve misfolded secretory proteins that have escaped from the ER.Molecular biology of the cell · 2025Article
- Article
- Epstein-Barr virus BALF0/1 subverts the Caveolin and ERAD pathways to target B cell receptor complexes for degradation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Determinants of chemoselectivity in ubiquitination by the J2 family of ubiquitin-conjugating enzymes.The EMBO journal · 2024Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Misfolded proteins of the endoplasmic reticulum (ER) are retrotranslocated into the cytosol, polyubiquitinated, and degraded by the proteasome, a process called ER-associated protein degradation (ERAD). Here, we use purified components from Saccharomyces cerevisiae to analyze the mechanism of retrotranslocation of luminal substrates (ERAD-L), recapitulating key steps in a basic process in which the ubiquitin ligase Hrd1p is the only required membrane protein. We show that Hrd1p interacts with substrate through its membrane-spanning domain and discriminates misfolded from folded polypeptides. Both Hrd1p and substrate are polyubiquitinated, resulting in the binding of Cdc48p ATPase complex. Subsequently, ATP hydrolysis by Cdc48p releases substrate from Hrd1p. Finally, ubiquitin chains are trimmed by the deubiquitinating enzyme Otu1p, which is recruited and activated by the Cdc48p complex. Cdc48p-dependent membrane extraction of polyubiquitinated proteins can be reproduced with reconstituted proteoliposomes. Our results suggest a model for retrotranslocation in which Hrd1p forms a membrane conduit for misfolded proteins.
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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.