Evidence map›Paper›PMID 20975039›Full record

ArticleThe Journal of experimental medicine2010

Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival.

Véronique Witko-Sarsat, Julie Mocek, Dikra Bouayad, Nicola Tamassia, Jean-Antoine Ribeil, Céline Candalh, Noélie Davezac, Nathalie Reuter, Luc Mouthon, Olivier Hermine and 2 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04970225 (Functional and Phenotypic Characteristics of Blood Neutrophils in Cystic Fibrosis), which is not on this map. Cited by 95 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing 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.

NCT04970225 nacompletednot on this mapstarted 2021, after this paper: background citation

Functional and Phenotypic Characteristics of Blood Neutrophils in Cystic Fibrosis

TypeinterventionalSponsorAssistance Publique - Hôpitaux de ParisRan2021 to 2025Enrolled47ConditionsCystic FibrosisArms1 blood sample, 2 blood samples
3 · Its place in the literature

Who cites it

95 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.

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  10. Cytosolic proliferating cell nuclear antigen (PCNA) orchestrates neutrophil hyperactivation in COVID-19.Proceedings of the National Academy of Sciences of the United States of America · 2025
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35 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

12 authors at 7 institutions in 4 countries.

Véronique Witko-SarsatInstitut National de la Santé et de la Recherche Médicale Unité 1016, 75014 Paris, France. veronique.witko@inserm.fr
Julie Mocek
Dikra Bouayad
Nicola Tamassia
Jean-Antoine Ribeil
Céline Candalh
Noélie Davezac
Nathalie Reuter
Luc Mouthon
Olivier Hermine
Magali Pederzoli-Ribeil
Marco A Cassatella
Inserm · FRInstitut Cochin · FRUniversity of Verona · ITCentre National pour la Recherche Scientifique et Technique (CNRST) · MAUniversité Paris Cité · FRUniversité Toulouse III - Paul Sabatier · FRUniversity of Bergen · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neutrophil apoptosis is a highly regulated process essential for inflammation resolution, the molecular mechanisms of which are only partially elucidated. In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells. We show that mature neutrophils, despite their inability to proliferate, express high levels of PCNA exclusively in their cytosol and constitutively associated with procaspases, presumably to prevent their activation. Notably, cytosolic PCNA abundance decreased during apoptosis, and increased during in vitro and in vivo exposure to the survival factor granulocyte colony-stimulating factor (G-CSF). Peptides derived from the cyclin-dependent kinase inhibitor p21, which compete with procaspases to bind PCNA, triggered neutrophil apoptosis thus demonstrating that specific modification of PCNA protein interactions affects neutrophil survival. Furthermore, PCNA overexpression rendered neutrophil-differentiated PLB985 myeloid cells significantly more resistant to TNF-related apoptosis-inducing ligand- or gliotoxin-induced apoptosis. Conversely, a decrease in PCNA expression after PCNA small interfering RNA transfection sensitized these cells to apoptosis. Finally, a mutation in the PCNA interdomain-connecting loop, the binding site for many partners, significantly decreased the PCNA-mediated antiapoptotic effect. These results identify PCNA as a regulator of neutrophil lifespan, thereby highlighting a novel target to potentially modulate pathological inflammation.

Indexed as

ApoptosisCaspase 3Caspase 9Cell DifferentiationCell NucleusCell SurvivalCyclin-Dependent Kinase Inhibitor p21CytoplasmHumansNeutrophilsPeptide FragmentsProliferating Cell Nuclear AntigenRNA, Small InterferingCaspase 3Caspase 9CDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21Peptide FragmentsProliferating Cell Nuclear AntigenRNA, Small Interfering

Identifiers

PMID20975039
PMCPMC2989777
OpenAlexW2167918360

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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Registered trials

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.