ArticleNature structural & molecular biology2011
Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant α-1 antitrypsin from the endoplasmic reticulum.
Article in Nature structural & molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 187 citations in OpenAlex.
- The polymerized protein response (PPR) is activated by genetic variants that polymerize in the ER and is mediated by NFκBp50.Nature communications · 2026Article
- The Hrd1-Mediated ERAD Pathway in Plants: Conserved Principles and Plant-Specific Innovations.International journal of molecular sciences · 2026Review
- Cryo-EM structure of the human Derlin-1/p97 complex reveals a hexameric channel in ERAD.Communications biology · 2025Article
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- p.Phe508del-CFTR Trafficking: A Protein Quality Control Perspective Through UPR, UPS, and Autophagy.International journal of molecular sciences · 2025Review
- Article
- DERL3 exacerbates glioblastoma malignancy through endoplasmic reticulum stress-dependent mechanisms.American journal of cancer research · 2025Article
- Evaluating the impact of the membrane thickness on the function of the intramembrane protease GlpG.Biophysical journal · 2024Article
- The Dsc complex and its role in Golgi quality control.Biochemical Society transactions · 2024Review
- Genome-wide identification, gene expression and haplotype analysis of the rhomboid-like gene family in wheat (Triticum aestivum L.).The plant genome · 2024Article
- The derlin Dfm1 couples retrotranslocation of a folded protein domain to its proteasomal degradation.The Journal of cell biology · 2024Article
- Advances in the study of protein folding and endoplasmic reticulum-associated degradation in mammal cells.Journal of Zhejiang University. Science. B · 2024Review
- Mechanisms of substrate processing during ER-associated protein degradation.Nature reviews. Molecular cell biology · 2023Review
- The cryo-EM structure of the human ERAD retrotranslocation complex.Science advances · 2023Article
- Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- An ERAD-independent role for rhomboid pseudoprotease Dfm1 in mediating sphingolipid homeostasis.The EMBO journal · 2023Article
- The Role of the Rhomboid Superfamily in ER Protein Quality Control: From Mechanisms and Functions to Diseases.Cold Spring Harbor perspectives in biology · 2023Review
- Noncanonical Form of ERAD Regulates Cardiac Hypertrophy.Circulation · 2023Article
- Yeast derlin Dfm1 employs a chaperone-like function to resolve misfolded membrane protein stress.PLoS biology · 2023Article
- Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The degradation of misfolded secretory proteins is ultimately mediated by the ubiquitin-proteasome system in the cytoplasm, therefore endoplasmic reticulum-associated degradation (ERAD) substrates must be dislocated across the ER membrane through a process driven by the AAA ATPase p97/VCP. Derlins recruit p97/VCP and have been proposed to be part of the dislocation machinery. Here we report that Derlins are inactive members of the rhomboid family of intramembrane proteases and bind p97/VCP through C-terminal SHP boxes. Human Derlin-1 harboring mutations within the rhomboid domain stabilized mutant α-1 antitrypsin (NHK) at the cytosolic face of the ER membrane without disrupting the p97/VCP interaction. We propose that substrate interaction and p97/VCP recruitment are separate functions that are essential for dislocation and can be assigned respectively to the rhomboid domain and the C terminus of Derlin-1. These data suggest that intramembrane proteolysis and protein dislocation share unexpected mechanistic features.
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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.