Evidence map›Paper›PMID 40132591›Full record

ArticleCell host & microbe2025

Transcriptional repressor Capicua is a gatekeeper of cell-intrinsic interferon responses.

Senthamizharasi Manivasagam, Julianna Han, Athmane Teghanemt, Henry Keen, Boopathi Sownthirarajan, Boyang Cheng, Abhiraj Singh, Abigail Lewis, Olivia A Vogel, Gayathri Loganathan and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell host & microbe, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Genetic mechanisms of resistance to targeted KRAS inhibition.bioRxiv : the preprint server for biology · 2025
    Article
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.

Senthamizharasi ManivasagamDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Julianna HanDepartment of Microbiology, University of Chicago, Chicago, IL, USA.
Athmane TeghanemtDepartment of Internal Medicine, University of Iowa, Iowa City, IA, USA.
Henry KeenBioinformatics Division of the Iowa Institute of Human Genetics, University of Iowa, Iowa City, IA, USA.
Boopathi SownthirarajanDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Boyang ChengDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Abhiraj SinghDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Abigail LewisDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Olivia A VogelDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA; Department of Microbiology, University of Chicago, Chicago, IL, USA.
Gayathri LoganathanDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Lei HuangCenter for Research Informatics, The University of Chicago, Chicago, IL 60637, USA.
Maryline PanisDepartment of Microbiology, New York University, New York, NY, USA.
David K MeyerholzDepartment of Pathology, University of Iowa, Iowa City, IA, USA.
Benjamin tenOeverDepartment of Microbiology, New York University, New York, NY, USA.
Jasmine T PerezDepartment of Microbiology, University of Chicago, Chicago, IL, USA.
Santhakumar ManicassamyGeorgia Cancer Center, Department of Medicine, Augusta University, Augusta, GA, USA.
Priya D IssureeDepartment of Internal Medicine, University of Iowa, Iowa City, IA, USA. Electronic address: priya-issuree@uiowa.edu.
Balaji ManicassamyDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA. Electronic address: balaji-manicassamy@uiowa.edu.

Funding

Molecular And Cellular Biology Training ProgramT32GM007183 · NIGMS · UNIVERSITY OF CHICAGO · PI GLICK, BENJAMIN S, RICE, PHOEBE A · 1985 to 2021
$23.9M
Regulation of innate antiviral responses by the DNA-binding transcriptional repressor complex CIC-ATXN1/LR01AI165932 · NIAID · UNIVERSITY OF IOWA · PI Balaji Manicassamy · 2022 to 2026
$3.0M
Modulation of Influenza Virus Replication and Fitness by Adenosine DeaminasesR01AI123359 · NIAID · UNIVERSITY OF IOWA · PI MANICASSAMY, BALAJI · 2016 to 2020
$1.9M
Regulation of colitis associated with acute kidney injury by the Wnt pathwayR01DK123360 · NIDDK · AUGUSTA UNIVERSITY · PI MANICASSAMY, SANTHAKUMAR · 2020 to 2023
$1.4M
Connecting epigenetic programming of T cells with molecular traits of the immune system in health and diseaseR35GM154831 · NIGMS · UNIVERSITY OF IOWA · PI Priya Issuree · 2024 to 2026
$1.2M
NIAID NIH HHS R01 AI123359NIAID NIH HHS R01 AI165932NIDDK NIH HHS R01 DK123360NIGMS NIH HHS R35 GM154831NIGMS NIH HHS T32 GM007183
6 · The paper itself

Abstract

Early detection of viral infection and rapid activation of host antiviral defenses through transcriptional upregulation of interferons (IFNs) and IFN-stimulated genes (ISGs) are critical for controlling infection. However, aberrant production of IFN in the absence of viral infection leads to auto-inflammation and can be detrimental to the host. Here, we show that the DNA-binding transcriptional repressor complex composed of Capicua (CIC) and Ataxin-1 like (ATXN1L) binds to an 8-nucleotide motif near IFN and ISG promoters and prevents erroneous expression of inflammatory genes under homeostasis in humans and mice. By contrast, during respiratory viral infection, activation of the mitogen-activated protein kinase (MAPK) pathway results in rapid degradation of the CIC-ATXN1L complex, thereby relieving repression and allowing for robust induction of IFN and ISGs. Together, our studies define a new paradigm for host regulation of IFN and ISGs through the evolutionarily conserved CIC-ATXN1L transcriptional repressor complex during homeostasis and viral infection.

Indexed as

InterferonsRepressor ProteinsAnimalsCo-Repressor ProteinsGene Expression RegulationHumansMiceMice, Inbred C57BLPromoter Regions, GeneticCIC protein, humanCo-Repressor ProteinsInterferonsRepressor ProteinsATXN1Lcell-intrinsic antiviral responsesCICIAVIFNinfluenza virusinterferoninterferon-stimulated genesISGvirus-host interactions

Identifiers

PMID40132591
PMCPMC11985295

What Socratic 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 Socratic graph.