Evidence map›Paper›PMID 38722278›Full record

ArticleThe Journal of cell biology2024

HERC3 facilitates ERAD of select membrane proteins by recognizing membrane-spanning domains.

Yuka Kamada, Yuko Ohnishi, Chikako Nakashima, Aika Fujii, Mana Terakawa, Ikuto Hamano, Uta Nakayamada, Saori Katoh, Noriaki Hirata, Hazuki Tateishi and 4 more

Abstract read
In one paragraph

Article in The Journal of cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. CaNature cell biology · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Membrane Contact Sites in Proteostasis and ER Stress Response.Contact (Thousand Oaks (Ventura County, Calif.))
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Yuka KamadaDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0009-0006-6746-9112
Yuko OhnishiDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0009-0007-8058-9642
Chikako NakashimaDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0009-0002-7181-4354
Aika FujiiDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0009-0005-5599-4932
Mana TerakawaDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0009-0000-9280-1179
Ikuto HamanoDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0009-0003-1483-5666
Uta NakayamadaDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0009-0006-4984-8485
Saori KatohDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0009-0007-9967-488X
Noriaki HirataDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0009-0001-7213-0555
Hazuki TateishiDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0009-0005-1787-8092
Ryosuke FukudaDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0009-0002-2352-4774
Hirotaka TakahashiDivision of Cell-Free Sciences, Proteo-Science Center (PROS), Ehime University, Matsuyama, Japan.ORCID 0000-0002-1278-416X
Gergely L LukacsDepartment of Physiology, McGill University, Montréal, Canada.ORCID 0000-0003-0900-0675
Tsukasa OkiyonedaDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Japan.ORCID 0000-0002-5175-2224

Funding

Japan Agency for Medical Research and Development JP23fk0210086h0003Japan Society for the Promotion of Science 21H00294Kwansei Gakuin UniversityTakeda Science Foundation
6 · The paper itself

Abstract

Aberrant proteins located in the endoplasmic reticulum (ER) undergo rapid ubiquitination by multiple ubiquitin (Ub) E3 ligases and are retrotranslocated to the cytosol as part of the ER-associated degradation (ERAD). Despite several ERAD branches involving different Ub E3 ligases, the molecular machinery responsible for these ERAD branches in mammalian cells remains not fully understood. Through a series of multiplex knockdown/knockout experiments with real-time kinetic measurements, we demonstrate that HERC3 operates independently of the ER-embedded ubiquitin ligases RNF5 and RNF185 (RNF5/185) to mediate the retrotranslocation and ERAD of misfolded CFTR. While RNF5/185 participates in the ERAD process of both misfolded ABCB1 and CFTR, HERC3 uniquely promotes CFTR ERAD. In vitro assay revealed that HERC3 directly interacts with the exposed membrane-spanning domains (MSDs) of CFTR but not with the MSDs embedded in liposomes. Therefore, HERC3 could play a role in the quality control of MSDs in the cytoplasm and might be crucial for the ERAD pathway of select membrane proteins.

Indexed as

Endoplasmic Reticulum-Associated DegradationMembrane ProteinsUbiquitin-Protein LigasesCystic Fibrosis Transmembrane Conductance RegulatorDNA-Binding ProteinsEndoplasmic ReticulumGuanine Nucleotide Exchange FactorsHEK293 CellsHeLa CellsHumansProtein BindingProtein DomainsProtein FoldingUbiquitinationCystic Fibrosis Transmembrane Conductance RegulatorDNA-Binding ProteinsGuanine Nucleotide Exchange FactorsHERC3 protein, humanMembrane ProteinsUbiquitin-Protein Ligases

Identifiers

PMID38722278
PMCPMC11082371

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.