A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity

Vinuesa, Carola G.; Cook, Matthew C.; Angelucci, Constanza; Athanasopoulos, Vicki; Rui, Lixin; Hill, Kim M.; Yu, Di; Domaschenz, Heather; Whittle, Belinda; Lambe, Teresa; Roberts, Ian S.; Copley, Richard R.; Bell, John I.; Cornall, Richard J.; Goodnow, Christopher C.

doi:10.1038/nature03555

Cited by 862T-cell and B-cell ImmunologySystemic Lupus Erythematosus ResearchDiabetes and associated disorders

A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity

Vinuesa, Carola G., Cook, Matthew C., Angelucci, Constanza, Athanasopoulos, Vicki, Rui, Lixin, Hill, Kim M., Yu, Di, Domaschenz, Heather +7 more·2005·Nature

DOI 10.1038/nature03555

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Abstract

Despite the sequencing of the human and mouse genomes, few genetic mechanisms for protecting against autoimmune disease are currently known. Here we systematically screen the mouse genome for autoimmune regulators to isolate a mouse strain, sanroque, with severe autoimmune disease resulting from a single recessive defect in a previously unknown mechanism for repressing antibody responses to self. The sanroque mutation acts within mature T cells to cause formation of excessive numbers of follicular helper T cells and germinal centres. The mutation disrupts a repressor of ICOS, an essential co-stimulatory receptor for follicular T cells, and results in excessive production of the cytokine interleukin-21. sanroque mice fail to repress diabetes-causing T cells, and develop high titres of autoantibodies and a pattern of pathology consistent with lupus. The causative mutation is in a gene of previously unknown function, roquin (Rc3h1), which encodes a highly conserved member of the RING-type ubiquitin ligase protein family. The Roquin protein is distinguished by the presence of a CCCH zinc-finger found in RNA-binding proteins, and localization to cytosolic RNA granules implicated in regulating messenger RNA translation and stability.

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RC3H1 encodes a protein that has an amino-terminal RING-1 zinc-finger, which is characteristic to that of the E3 ubiquitin ligase family.
“Interestingly, RC3H1 also encodes a protein that has an amino-terminal RING-1 zinc-finger, which is characteristic to that of the E3 ubiquitin ligase family.50”
From APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease (2016) · cites this paper as [50]

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Roquin Represses Autoimmune Responses
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Authors: Vinuesa, C. G., Cook, M. C., Angelucci, C., Athanasopoulos, V., Rui, L., Hill, K. M., Yu, D., Domaschenz, H., Whittle, B., Lambe, T., Roberts, I. S., Copley, R. R., Bell, J. I., Cornall, R. J., & Goodnow, C. C.
Affiliations: Australian National University (AU)
University of Oxford (GB)
John Radcliffe Hospital (GB)
Centre for Human Genetics (GB)
Corresponding author: Vinuesa, Carola G.
Goodnow, Christopher C.
ORCID: Vinuesa, Carola G.
Cook, Matthew C.
Angelucci, Constanza
Athanasopoulos, Vicki
Rui, Lixin
Yu, Di
Lambe, Teresa
Roberts, Ian S.
Copley, Richard R.
Bell, John I.
Cornall, Richard J.
Goodnow, Christopher C.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2005-05
Volume: 435
Issue: 7041
Pages: 452-458
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature03555
OpenAlex: W2031622194
Cited by: 862
References: 50
Citations by year: 2026: 9 · 2025: 11 · 2024: 28 · 2023: 21 · 2022: 24 · 2021: 46 · 2020: 33 · 2019: 50 · 2018: 43 · 2017: 34 · 2016: 61 · 2015: 54 · 2014: 60 · 2013: 64 · 2012: 50
FWCI: 14.78
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
ANU Open Research (Australian National University) (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords: Roquin, T follicular helper cells, germinal center, ICOS, IL-21, autoimmunity, lupus, diabetes mellitus, autoantibodies, self-tolerance, RNA granules, CCCH zinc finger, RNA-binding proteins, mRNA stability, T cell costimulation
MeSH terms: Amino Acid Sequence, Animals, Autoantibodies, Disease Models, Animal, Female, T-Lymphocytes, Helper-Inducer, Humans, Lupus Erythematosus, Systemic, Male, Molecular Sequence Data, Receptors, Antigen, T-Cell, Autoimmunity, Mutation, Missense, Ubiquitin-Protein Ligases, Cell Line, Tumor, Mice

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

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Record

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