Evidence map›Paper›PMID 19720873›Full record

ArticleThe Journal of cell biology2009

The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER.

Helen R Stagg, Mair Thomas, Dick van den Boomen, Emmanuel J H J Wiertz, Harry A Drabkin, Robert M Gemmill, Paul J Lehner

Open access · hybridAbstract read
In one paragraph

Article in The Journal of cell biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
8.3field-weighted citation impact, top 2% of its field
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

85 citing papers in PubMed, 148 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025
    Review
  5. Macrophage HM13/SPP Enhances Foamy Macrophage Formation and Atherogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. The Endoplasmic Reticulum and the Fidelity of Nascent Protein Localization.Cold Spring Harbor perspectives in biology · 2023
    Review
  12. Endoplasmic Reticulum-Associated Protein Degradation.Cold Spring Harbor perspectives in biology · 2022
    Review
  13. Viruses Hijack ERAD to Regulate Their Replication and Propagation.International journal of molecular sciences · 2022
    Review
  14. Article
  15. Article
  16. Review
  17. Hepatitis C virus modulates signal peptide peptidase to alter host protein processing.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  18. Article
  19. Article
  20. Review

25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

Helen R StaggCambridge Institute for Medical Research, University of Cambridge, Cambridge CB20XY, England, UK.
Mair Thomas
Dick van den Boomen
Emmanuel J H J Wiertz
Harry A Drabkin
Robert M Gemmill
Paul J Lehner
University of Cambridge · GBMedical University of South Carolina · USUniversity Medical Center Utrecht · NL

Funding

Medical Research Council G0600823Medical Research Council G9800943Wellcome Trust 084957
6 · The paper itself

Abstract

The US2 and US11 gene products of human cytomegalovirus promote viral evasion by hijacking the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. US2 and US11 initiate dislocation of newly translocated major histocompatibility complex class I (MHC I) from the ER to the cytosol for proteasome-mediated degradation, thereby decreasing cell surface MHC I. Despite being instrumental in elucidating the mammalian ERAD pathway, the responsible E3 ligase or ligases remain unknown. Using a functional small interfering RNA library screen, we now identify TRC8 (translocation in renal carcinoma, chromosome 8 gene), an ER-resident E3 ligase previously implicated as a hereditary kidney cancer gene, as required for US2-mediated MHC I ubiquitination. Depletion of TRC8 prevents MHC I ubiquitination and dislocation by US2 and restores cell surface MHC I. TRC8 forms an integral part of a novel multiprotein ER complex that contains MHC I, US2, and signal peptide peptidase. Our data show that the TRC8 E3 ligase is required for MHC I dislocation from the ER and identify a new complex associated with mammalian ERAD.

Indexed as

Major Histocompatibility ComplexAnimalsEndoplasmic ReticulumHeLa CellsHistocompatibility Antigens Class IHumansMutationReceptors, Cell SurfaceRecombinant Fusion ProteinsRNA InterferenceUbiquitinViral Envelope ProteinsHistocompatibility Antigens Class IReceptors, Cell SurfaceRecombinant Fusion ProteinsRNF139 protein, humanUbiquitinUS2 protein, VaricellovirusViral Envelope Proteins

Identifiers

PMID19720873
PMCPMC2742190
OpenAlexW1992315987

What OpenQuestion holds

Textmetadata
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.