ArticleCell reports2022
Rhomboid protease RHBDL4 promotes retrotranslocation of aggregation-prone proteins for degradation.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 33 citations in OpenAlex.
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Targeting the Membrane-Embedded Rhomboid Protease GlpG: A Multimodal Strategy for Inhibitor Discovery and Mechanistic Insight.Angewandte Chemie (International ed. in English) · 2026Article
- 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
- RHBDD1 induces cell cycle arrest in TP53-mutant NSCLC cells by promoting endoplasmic reticulum-associated degradation of p53 and DNA-PKcs.European journal of medical research · 2025Article
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- Loss of the APP regulator RHBDL4 preserves memory in an Alzheimer's disease mouse model.Cell death & disease · 2025Article
- 4-Oxo-β-lactams as Covalent Inhibitors of the Mitochondrial Intramembrane Protease PARL.ACS medicinal chemistry letters · 2024Article
- Evaluating the impact of the membrane thickness on the function of the intramembrane protease GlpG.Biophysical journal · 2024Article
- AnbioRxiv : the preprint server for biology · 2024Article
- Activity-Based Protein Profiling of RHBDL4 Reveals Proteolysis of the Enzyme and a Distinct Inhibitor Profile.ACS chemical biology · 2024Article
- ERLIN1/2 scaffolds bridge TMUB1 and RNF170 and restrict cholesterol esterification to regulate the secretory pathway.Life science alliance · 2024Article
- Genome-wide identification, gene expression and haplotype analysis of the rhomboid-like gene family in wheat (Triticum aestivum L.).The plant genome · 2024Article
- Proteotoxic stress and the ubiquitin proteasome system.Seminars in cell & developmental biology · 2024Review
- RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling.Nature communications · 2024Article
- The generation of detergent-insoluble clipped fragments from an ERAD substrate in mammalian cells.Scientific reports · 2023Article
- Mechanisms of substrate processing during ER-associated protein degradation.Nature reviews. Molecular cell biology · 2023Review
- ER-associated degradation in cystinosis pathogenesis and the prospects of precision medicine.The Journal of clinical investigation · 2023Article
- Yeast derlin Dfm1 employs a chaperone-like function to resolve misfolded membrane protein stress.PLoS biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Protein degradation is fundamentally important to ensure cell homeostasis. In the endoplasmic reticulum (ER), the ER-associated degradation (ERAD) pathway targets incorrectly folded and unassembled proteins for turnover by the cytoplasmic proteasome. Previously, we showed that the rhomboid protease RHBDL4, together with p97, mediates membrane protein degradation. However, whether RHBDL4 acts in concert with additional ERAD components is unclear, and its full substrate spectrum remains to be defined. Here, we show that, in addition to membrane proteins, RHBDL4 cleaves aggregation-prone luminal ERAD substrates. Since mutations of the RHBDL4 rhomboid domain led to stabilization of substrates at the cytoplasmic side, we hypothesize that, analogous to the homolog ERAD factor derlin, RHBDL4 is directly involved in substrate retrotranslocation. RHBDL4's interaction with the erlin ERAD complex and reciprocal interaction of rhomboid substrates with erlins suggest that RHBDL4 and erlins form a complex that clips substrates and thereby rescues aggregation-prone peptides in the ER from aggregation.
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.