Evidence map›Paper›PMID 22942423›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2012

The small ubiquitin-like modifier-deconjugating enzyme sentrin-specific peptidase 1 switches IFN regulatory factor 8 from a repressor to an activator during macrophage activation.

Tsung-Hsien Chang, Songxiao Xu, Prafullakumar Tailor, Tomohiko Kanno, Keiko Ozato

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

35 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. Review
  3. Unconventional posttranslational modification in innate immunity.Cellular and molecular life sciences : CMLS · 2024
    Review
  4. Article
  5. A lncRNA identifieseLife · 2023
    Article
  6. Review
  7. Review
  8. SUMOylation targeting mitophagy in cardiovascular diseases.Journal of molecular medicine (Berlin, Germany) · 2022
    Review
  9. Article
  10. Review
  11. SUMO and SUMOylation Pathway at the Forefront of Host Immune Response.Frontiers in cell and developmental biology · 2021
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  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

5 authors at 3 institutions in 3 countries.

Tsung-Hsien ChangProgram in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Songxiao Xu
Prafullakumar Tailor
Tomohiko Kanno
Keiko Ozato
National Institute of Child Health · HUNational Institute of Child Health · PKNational Institutes of Health · US

Funding

Chromatin and epigenetic memory ZIAHD008815 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI OZATO, KEIKO · 2009 to 2025
$16.2M
Gene Regulation In The Immune SystemZIAHD001310 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI OZATO, KEIKO · 2009 to 2025
$15.0M
GENE REGULATION IN THE IMMUNE SYSTEMZ01HD001310 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI OZATO, KEIKO · 1988 to 2008
$1.8M
Intramural NIH HHS Z01 HD001310Intramural NIH HHS ZIA HD008815
6 · The paper itself

Abstract

Macrophages, when activated by IFN-γ and TLR signaling, elicit innate immune responses. IFN regulatory factor 8 (IRF8) is a transcription factor that facilitates macrophage activation and innate immunity. We show that, in resting macrophages, some IRF8 is conjugated to small ubiquitin-like modifiers (SUMO) 2/3 through the lysine residue 310. SUMO3-conjugated IRF8 failed to induce IL12p40 and other IRF8 target genes, consistent with SUMO-mediated transcriptional repression reported for other transcription factors. SUMO3-conjugated IRF8 showed reduced mobility in live nuclei and bound poorly to the IL12p40 gene. However, macrophage activation caused a sharp reduction in the amount of SUMOylated IRF8. This reduction coincided with the induction of a deSUMOylating enzyme, sentrin-specific peptidase 1 (SENP1), in activated macrophages. In transfection analysis, SENP1 removed SUMO3 from IRF8 and enhanced expression of IL12p40 and other target genes. Conversely, SENP1 knockdown repressed IRF8 target gene expression. In parallel with IRF8 deSUMOylation, macrophage activation led to the induction of proteins active in the SUMO pathway and caused a global shift in nuclear protein SUMOylation patterns. Together, the IRF8 SUMO conjugation/deconjugation switch is part of a larger transition in SUMO modifications that takes place upon macrophage activation, serving as a mechanism to trigger innate immune responses.

Indexed as

AnimalsCells, CulturedCysteine EndopeptidasesEndopeptidasesHEK293 CellsHumansInterferon Regulatory Factor-8Interferon Regulatory FactorsInterleukin-12 Subunit p40LysineMacrophage ActivationMacrophagesMiceNIH 3T3 CellsProtein BindingRepressor ProteinsCysteine EndopeptidasesEndopeptidasesInterferon Regulatory Factor-8Interferon Regulatory FactorsInterleukin-12 Subunit p40LysineRepressor ProteinsSENP1 protein, humanSenp1 protein, mouseSmall Ubiquitin-Related Modifier ProteinsSUMO2 protein, humanSUMO2 protein, mouseSUMO3 protein, humanSumo3 protein, mouseUbiquitins

Identifiers

PMID22942423
PMCPMC4158928
OpenAlexW2146229668

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.