Evidence map›Paper›PMID 38568811›Full record

ArticleCell reports2024

The Legionella pneumophila effector DenR hijacks the host NRas proto-oncoprotein to downregulate MAPK signaling.

Stephanie S Lehman, Chad D Williamson, Trisha Tucholski, Nicole A Ellis, Sabrina Bouchard, Michal Jarnik, Morgan Allen, Aleksandra Nita-Lazar, Matthias P Machner

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
3.1field-weighted citation impact, top 11% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Experimental Approaches to Visualize Effector Protein Translocation During Host-Pathogen Interactions.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  5. 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

9 authors at 2 institutions in 1 country.

Stephanie S LehmanDivision of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Chad D WilliamsonDivision of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Trisha TucholskiFunctional Cellular Networks Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Nicole A EllisDivision of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Sabrina BouchardDivision of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Michal JarnikDivision of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Morgan AllenDivision of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Aleksandra Nita-LazarFunctional Cellular Networks Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Matthias P MachnerDivision of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: machnerm@nih.gov.
National Institutes of Health · USEunice Kennedy Shriver National Institute of Child Health and Human Development · US

Funding

Virulence strategies of the respiratory pathogen Legionella pneumophilaZIAHD008893 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MACHNER, MATTHIAS · 2010 to 2025
$19.6M
Protein Modifications Involved in Cell SignalingZIAAI001084 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NITA-LAZAR, ALEKSANDRA · 2009 to 2025
$11.4M
Absolute Quantification of Molecular Representation and InteractionZIAAI001085 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NITA-LAZAR, ALEKSANDRA · 2009 to 2025
$10.7M
Intramural NIH HHS ZIA AI001085Intramural NIH HHS ZIA HD008893
6 · The paper itself

Abstract

Small GTPases of the Ras subfamily are best known for their role as proto-oncoproteins, while their function during microbial infection has remained elusive. Here, we show that Legionella pneumophila hijacks the small GTPase NRas to the Legionella-containing vacuole (LCV) surface. A CRISPR interference screen identifies a single L. pneumophila effector, DenR (Lpg1909), required for this process. Recruitment is specific for NRas, while its homologs KRas and HRas are excluded from LCVs. The C-terminal hypervariable tail of NRas is sufficient for recruitment, and interference with either NRas farnesylation or S-acylation sites abrogates recruitment. Intriguingly, we detect markers of active NRas signaling on the LCV, suggesting it acts as a signaling platform. Subsequent phosphoproteomics analyses show that DenR rewires the host NRas signaling landscape, including dampening of the canonical mitogen-activated protein kinase pathway. These results provide evidence for L. pneumophila targeting NRas and suggest a link between NRas GTPase signaling and microbial infection.

Indexed as

Bacterial ProteinsGTP PhosphohydrolasesLegionella pneumophilaMAP Kinase Signaling SystemMembrane ProteinsDown-RegulationHEK293 CellsHumansLegionnaires' DiseaseProto-Oncogene Proteins p21(ras)VacuolesBacterial ProteinsGTP PhosphohydrolasesMembrane ProteinsNRAS protein, humanProto-Oncogene Proteins p21(ras)cancerCP: Microbiologyintracellular pathogenpalmitoylationtype IV secretion systemvirulence

Identifiers

PMID38568811
PMCPMC11141579
OpenAlexW4393559294

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.