Evidence map›Paper›PMID 29351849›Full record

ArticleMolecular cell2018

The Dfm1 Derlin Is Required for ERAD Retrotranslocation of Integral Membrane Proteins.

Sonya Neal, Philipp A Jaeger, Sascha H Duttke, Christopher Benner, Christopher K Glass, Trey Ideker, Randolph Y Hampton

Erratum issuedAbstract read
In one paragraph

Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed.

  1. Review
  2. Competition between Der1 and ERAD-M substrates controls Hrd1 complex function.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Proteotoxic stress and the ubiquitin proteasome system.Seminars in cell & developmental biology · 2024
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Endoplasmic Reticulum-Associated Protein Degradation.Cold Spring Harbor perspectives in biology · 2022
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Sonya NealDivision of Biological Sciences, the Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093, USA.
Philipp A JaegerDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Biocipher(X), Inc., San Diego, CA 92121, USA.
Sascha H DuttkeDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Christopher BennerDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Christopher K GlassDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Trey IdekerDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: tideker@ucsd.edu.
Randolph Y HamptonDivision of Biological Sciences, the Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: rhampton@ucsd.edu.

Funding

A Systems Approach to Mapping the DNA Damage ResponseR01ES014811 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2005 to 2021
$8.6M
PROTEIN DEGRADATION AND CHOLESTEROL REGULATIONR01DK051996 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMPTON, RANDOLPH Y. · 1997 to 2024
$5.2M
Comparative Analysis of Genetic Interaction NetworksR01GM084279 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY, KROGAN, NEVAN J · 2008 to 2017
$3.9M
Protein degradation and cholesterol regulationR37DK051996 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMPTON, RANDOLPH Y. · 2012 to 2020
$3.2M
The Discovery of Molecules and Mechanisms of the Rhomboid SuperfamilyR35GM133565 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Sonya Elina Neal · 2019 to 2026
$2.9M
Interleukin 18 and Atherosclerosis during StressR21HL088083 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI CONTI, BRUNO · 2008 to 2009
$520k
An integrative multi-phenotype pipeline for drug evaluation, pharmacogenomics, and attribute predictionR41TR001908 · NCATS · PHENVOGEN, LLC · PI JAEGER, PHILIPP · 2017 to 2017
$225k
Discovering the machinery and mechanism of ERAD-M retrotranslocationF32GM111024 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NEAL, SONYA ELINA · 2014 to 2016
$164k
NCATS NIH HHS R41 TR001908NHLBI NIH HHS R21 HL088083NIDDK NIH HHS R01 DK051996NIDDK NIH HHS R37 DK051996NIEHS NIH HHS R01 ES014811NIGMS NIH HHS F32 GM111024NIGMS NIH HHS R01 GM084279NIGMS NIH HHS R35 GM133565
6 · The paper itself

Abstract

Endoplasmic reticulum (ER)-associated degradation (ERAD) removes misfolded proteins from the ER membrane and lumen by the ubiquitin-proteasome pathway. Retrotranslocation of ubiquitinated substrates to the cytosol is a universal feature of ERAD that requires the Cdc48 AAA-ATPase. Despite intense efforts, the mechanism of ER exit, particularly for integral membrane (ERAD-M) substrates, has remained unclear. Using a self-ubiquitinating substrate (SUS), which undergoes normal retrotranslocation independently of known ERAD factors, and the new SPOCK (single plate orf compendium kit) micro-library to query all yeast genes, we found the rhomboid derlin Dfm1 was required for retrotranslocation of both HRD and DOA ERAD pathway integral membrane substrates. Dfm1 recruited Cdc48 to the ER membrane with its unique SHP motifs, and it catalyzed substrate extraction through its conserved rhomboid motifs. Surprisingly, dfm1Δ can undergo rapid suppression, restoring wild-type ERAD-M. This unexpected suppression explained earlier studies ruling out Dfm1, and it revealed an ancillary ERAD-M retrotranslocation pathway requiring Hrd1.

Indexed as

Adenosine TriphosphatasesCell Cycle ProteinsCytosolEndoplasmic ReticulumEndoplasmic Reticulum-Associated DegradationMembrane ProteinsProteasome Endopeptidase ComplexSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitinUbiquitinationUbiquitin-Protein LigasesValosin Containing ProteinAdenosine TriphosphatasesCDC48 protein, S cerevisiaeCell Cycle ProteinsDER1 protein, S cerevisiaeDfm1 protein, S cerevisiaeMembrane ProteinsProteasome Endopeptidase ComplexSaccharomyces cerevisiae ProteinsUbiquitinUbiquitin-Protein LigasesValosin Containing ProteinCdc48derlinsDfm1DOAendoplasmic reticulumERERADHMG-CoA reductaseHRDretrotranslocationrhomboid

Identifiers

PMID29351849
PMCPMC6049073

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.