Evidence map›Paper›PMID 38787820›Full record

ArticlePloS one2024

Proinsulin degradation and presentation of a proinsulin B-chain autoantigen involves ER-associated protein degradation (ERAD)-enzyme UBE2G2.

Tom Cremer, Hanneke Hoelen, Michael L van de Weijer, George M Janssen, Ana I Costa, Peter A van Veelen, Robert Jan Lebbink, Emmanuel J H J Wiertz

Abstract read
In one paragraph

Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Regulation of placental development and function by ubiquitination.Molecular medicine (Cambridge, Mass.) · 2025
    Review
  4. Review
  5. Review
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

8 authors.

Tom CremerDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0002-5480-574X
Hanneke HoelenDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Michael L van de WeijerSir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-0954-0228
George M JanssenDepartment of Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
Ana I CostaDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Peter A van VeelenDepartment of Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
Robert Jan LebbinkDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0002-1981-0420
Emmanuel J H J WiertzDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0001-6080-7058

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Type 1 diabetes (T1D) is characterized by HLA class I-mediated presentation of autoantigens on the surface of pancreatic β-cells. Recognition of these autoantigens by CD8+ T cells results in the destruction of pancreatic β-cells and, consequently, insulin deficiency. Most epitopes presented at the surface of β-cells derive from the insulin precursor molecule proinsulin. The intracellular processing pathway(s) involved in the generation of these peptides are poorly defined. In this study, we show that a proinsulin B-chain antigen (PPIB5-14) originates from proinsulin molecules that are processed by ER-associated protein degradation (ERAD) and thus originate from ER-resident proteins. Furthermore, screening genes encoding for E2 ubiquitin conjugating enzymes, we identified UBE2G2 to be involved in proinsulin degradation and subsequent presentation of the PPIB10-18 autoantigen. These insights into the pathway involved in the generation of insulin-derived peptides emphasize the importance of proinsulin processing in the ER to T1D pathogenesis and identify novel targets for future T1D therapies.

Indexed as

AutoantigensEndoplasmic Reticulum-Associated DegradationProinsulinProteolysisUbiquitin-Conjugating EnzymesAntigen PresentationDiabetes Mellitus, Type 1HumansInsulin-Secreting CellsAutoantigensProinsulinUBE2G2 protein, humanUbiquitin-Conjugating Enzymes

Identifiers

PMID38787820
PMCPMC11125532

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Registered trials

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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.