Evidence map›Paper›PMID 26488816›Full record

ArticleImmunity2015

Ubiquitin Ligase TRIM62 Regulates CARD9-Mediated Anti-fungal Immunity and Intestinal Inflammation.

Zhifang Cao, Kara L Conway, Robert J Heath, Jason S Rush, Elizaveta S Leshchiner, Zaida G Ramirez-Ortiz, Natalia B Nedelsky, Hailiang Huang, Aylwin Ng, Agnès Gardet and 8 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% 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

83 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Pharmacological targeting of adaptor proteins in chronic inflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
    Review
  14. Article
  15. Review
  16. Article
  17. CARD9 in the pathogenesis of axial spondyloarthritis.Best practice & research. Clinical rheumatology · 2024
    Review
  18. Article
  19. Review
  20. Article

23 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

18 authors at 6 institutions in 3 countries.

Zhifang CaoGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Kara L ConwayGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Robert J HeathGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jason S RushBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Elizaveta S LeshchinerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Zaida G Ramirez-OrtizCenter for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Natalia B NedelskyGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Hailiang HuangBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Aylwin NgGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Agnès GardetGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Shih-Chin ChengDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen 6525 GA, the Netherlands.
Alykhan F ShamjiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
John D RiouxResearch Center, Montreal Heart Institute and Université de Montréal, QC H1T 1C8, Canada.
Cisca WijmengaDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen T9700 RB, the Netherlands.
Mihai G NeteaDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen 6525 GA, the Netherlands.
Terry K MeansCenter for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Mark J DalyBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Ramnik J XavierGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: xavier@molbio.mgh.harvard.edu.
Broad Institute · USRadboud University Nijmegen · NLHarvard University · USMassachusetts General Hospital · USUniversité de Montréal · CAUniversity Medical Center Groningen · NL

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Curtis Huttenhower · 1991 to 2026
$35.3M
Universite de Montreal IBD Genetics Research CenterU01DK062432 · NIDDK · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI John D. Rioux · 2002 to 2026
$9.6M
ATG16L1 T300A: genetics to biologyR01DK097485 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI XAVIER, RAMNIK J · 2013 to 2021
$4.1M
Mechanisms of anti-fungal immunity mediated by SCARF1 and CD36R01AI084884 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI MEANS, TERRY K · 2010 to 2014
$2.1M
Genetics, Genes, and Pathways in Inflammatory Bowel Disease (IBD)RC1DK086502 · NIDDK · BROAD INSTITUTE, INC. · PI DALY, MARK JOSEPH, XAVIER, RAMNIK J · 2009 to 2010
$998k
Role of SCARF1 in Human LupusK01AR066716 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RAMIREZ-ORTIZ, ZAIDA GISELA · 2014 to 2019
$663k
NIAID NIH HHS AI084884NIAID NIH HHS R01 AI084884NIAMS NIH HHS AR066716NIAMS NIH HHS K01 AR066716NIDDK NIH HHS DK062432NIDDK NIH HHS DK086502NIDDK NIH HHS DK097485NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK097485NIDDK NIH HHS RC1 DK086502NIDDK NIH HHS U01 DK062432
6 · The paper itself

Abstract

CARD9 is a central component of anti-fungal innate immune signaling via C-type lectin receptors, and several immune-related disorders are associated with CARD9 alterations. Here, we used a rare CARD9 variant that confers protection against inflammatory bowel disease as an entry point to investigating CARD9 regulation. We showed that the protective variant of CARD9, which is C-terminally truncated, acted in a dominant-negative manner for CARD9-mediated cytokine production, indicating an important role for the C terminus in CARD9 signaling. We identified TRIM62 as a CARD9 binding partner and showed that TRIM62 facilitated K27-linked poly-ubiquitination of CARD9. We identified K125 as the ubiquitinated residue on CARD9 and demonstrated that this ubiquitination was essential for CARD9 activity. Furthermore, we showed that similar to Card9-deficient mice, Trim62-deficient mice had increased susceptibility to fungal infection. In this study, we utilized a rare protective allele to uncover a TRIM62-mediated mechanism for regulation of CARD9 activation.

Indexed as

Adjuvants, ImmunologicAnimalsCandidiasis, InvasiveCARD Signaling Adaptor ProteinsColitisCytokinesDendritic CellsGenes, DominantGenetic Predisposition to DiseaseHEK293 CellsHeLa CellsHumansInflammatory Bowel DiseasesMiceMice, 129 StrainMice, KnockoutAdjuvants, ImmunologicCARD9 protein, humanCard9 protein, mouseCARD Signaling Adaptor ProteinsCytokinesDear1 protein, mouseProtein IsoformsReceptors, AngiotensinReceptors, EndothelinRecombinant Fusion ProteinsTRIM62 protein, humanTripartite Motif ProteinsUbiquitin-Protein Ligases

Identifiers

PMID26488816
PMCPMC4672733
OpenAlexW2141727194

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.