Evidence map›Paper›PMID 34144993›Full record

ArticleScience advances2021

Systematic profiling of protein complex dynamics reveals DNA-PK phosphorylation of IFI16 en route to herpesvirus immunity.

Joshua L Justice, Michelle A Kennedy, Josiah E Hutton, Dawei Liu, Bokai Song, Brett Phelan, Ileana M Cristea

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.4field-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

39 citing papers in PubMed, 55 citations in OpenAlex.

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  18. When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024
    Review
  19. mViruses · 2024
    Review
  20. 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

7 authors at 1 institution in 1 country.

Joshua L JusticeDepartment of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.ORCID 0000-0003-1884-8555
Michelle A KennedyDepartment of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.ORCID 0000-0002-3179-2456
Josiah E HuttonDepartment of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.ORCID 0000-0002-5518-9651
Dawei LiuDepartment of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.ORCID 0000-0003-1911-9207
Bokai SongDepartment of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.ORCID 0000-0002-6643-9484
Brett PhelanDepartment of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.
Ileana M CristeaDepartment of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA. icristea@princeton.edu.ORCID 0000-0002-6533-2458
Princeton University · US

Funding

PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007388 · NIGMS · PRINCETON UNIVERSITY · PI CRISTEA, ILEANA M. · 1985 to 2022
$27.4M
Mechanisms mediating immune response upon sensing of nuclear viral DNAR01GM114141 · NIGMS · PRINCETON UNIVERSITY · PI CRISTEA, ILEANA M. · 2015 to 2023
$2.6M
NIGMS NIH HHS R01 GM114141NIGMS NIH HHS T32 GM007388
6 · The paper itself

Abstract

Dynamically shifting protein-protein interactions (PPIs) regulate cellular responses to viruses and the resulting immune signaling. Here, we use thermal proximity coaggregation (TPCA) mass spectrometry to characterize the on-off behavior of PPIs during infection with herpes simplex virus 1 (HSV-1), a virus with an ancient history of coevolution with hosts. Advancing the TPCA analysis to infer associations de novo, we build a time-resolved portrait of thousands of host-host, virus-host, and virus-virus PPIs. We demonstrate that, early in infection, the DNA sensor IFI16 recruits the active DNA damage response kinase, DNA-dependent protein kinase (DNA-PK), to incoming viral DNA at the nuclear periphery. We establish IFI16 T149 as a substrate of DNA-PK upon viral infection or DNA damage. This phosphorylation promotes IFI16-driven cytokine responses. Together, we characterize the global dynamics of PPIs during HSV-1 infection, uncovering the co-regulation of IFI16 and DNA-PK functions as a missing link in immunity to herpesvirus infection.

Indexed as

Herpes SimplexHerpesviridaeHerpesviridae InfectionsHerpesvirus 1, HumanHost-Pathogen InteractionsHumansNuclear ProteinsPhosphoproteinsPhosphorylationIFI16 protein, humanNuclear ProteinsPhosphoproteins

Identifiers

PMID34144993
PMCPMC8213230
OpenAlexW3169670957

What OpenQuestion holds

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LicenceCC BY-NC
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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.