ArticleMolecular and cellular biology2009
Contributions to neutropenia from PFAAP5 (N4BP2L2), a novel protein mediating transcriptional repressor cooperation between Gfi1 and neutrophil elastase.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells.The Journal of clinical investigation · 2015Trial
- Lineage-Specific Disruption of Hematopoiesis by Oxaliplatin: Mechanisms of Erythropoietin Resistance and Immune Suppression.Journal of hematology and oncology research · 2026Article
- EXO1 overexpression induces homologous recombination deficiency and enhances PARP inhibitor sensitivity in ER-positive breast cancer: modulation by N4BP2L2-Mediated restoration.Frontiers in cell and developmental biology · 2025Article
- 1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit.International journal of molecular sciences · 2024Article
- SpiderLearner: An ensemble approach to Gaussian graphical model estimation.Statistics in medicine · 2023Article
- Plasma circN4BP2L2 is a promising novel diagnostic biomarker for epithelial ovarian cancer.BMC cancer · 2022Article
- Neutrophil Elastase Defects in Congenital Neutropenia.Frontiers in immunology · 2021Review
- Serpin B1 defect and increased apoptosis of neutrophils in Cohen syndrome neutropenia.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Loss of Elongation-Like Factor 1 Spontaneously Induces Diverse, RNase H-Related Suppressor Mutations inGenetics · 2018Article
- Salivary biomarkers for the diagnosis and monitoring of neurological diseases.Biomedical journal · 2018Review
- Article
- The zinc finger transcription factor ZXDC activates CCL2 gene expression by opposing BCL6-mediated repression.Molecular immunology · 2013Article
- ELANE mutations in cyclic and severe congenital neutropenia: genetics and pathophysiology.Hematology/oncology clinics of North America · 2013Review
- Congenital neutropenia: diagnosis, molecular bases and patient management.Orphanet journal of rare diseases · 2011Review
- Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases.Pharmacological reviews · 2010Review
- Gfi1 and Gfi1b: key regulators of hematopoiesis.Leukemia · 2010Review
- Cyclic neutropenia associated with T cell immunity to granulocyte proteases and a double de novo mutation in GFI1, a transcriptional regulator of ELANE.British journal of haematology · 2010Article
- Gfi1-cells and circuits: unraveling transcriptional networks of development and disease.Current opinion in hematology · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
"Neutropenia" refers to deficient numbers of neutrophils, the most abundant type of white blood cell. Two main forms of inherited neutropenia are cyclic neutropenia, in which neutrophil counts oscillate with a 21-day frequency, and severe congenital neutropenia, in which static neutropenia may evolve at times into leukemia. Mutations of ELA2, encoding the protease neutrophil elastase, can cause both disorders. Among other genes, severe congenital neutropenia can also result from mutations affecting the transcriptional repressor Gfi1, one of whose genetic targets is ELA2, suggesting that the two act through similar mechanisms. In order to identify components of a common pathway regulating neutrophil production, we conducted yeast two-hybrid screens with Gfi1 and neutrophil elastase and detected a novel protein, PFAAP5 (also known as N4BP2L2), interacting with both. Expression of PFAAP5 allows neutrophil elastase to potentiate the repression of Gfi1 target genes, as determined by reporter assays, RNA interference, chromatin immunoprecipitation, and impairment of neutrophil differentiation in HSCs with PFAAP5 depletion, thus delineating a mechanism through which neutrophil elastase could regulate its own synthesis. Our findings are consistent with theoretical models of cyclic neutropenia proposing that its periodicity can be explained through disturbance of a feedback circuit in which mature neutrophils inhibit cell proliferation, thereby homeostatically regulating progenitor populations.
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What OpenQuestion holds
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.