ArticleMolecular and cellular biology2004
A novel notch protein, N2N, targeted by neutrophil elastase and implicated in hereditary neutropenia.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
27 citing papers in PubMed, 54 citations in OpenAlex.
- NOTCH2NLA gene amplification is associated with poor prognosis in breast cancer.Discover oncology · 2026Article
- A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy.Acta pharmaceutica Sinica. B · 2023Article
- Comparative physiological anthropogeny: exploring molecular underpinnings of distinctly human phenotypes.Physiological reviews · 2023Review
- Article
- The Phenotypes and Mechanisms of NOTCH2NLC-Related GGC Repeat Expansion Disorders: a Comprehensive Review.Molecular neurobiology · 2022Review
- A Connectomic Hypothesis for the Hominization of the Brain.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Neutrophil Elastase Defects in Congenital Neutropenia.Frontiers in immunology · 2021Review
- Emodin inhibiting neutrophil elastase-induced epithelial-mesenchymal transition through Notch1 signalling in alveolar epithelial cells.Journal of cellular and molecular medicine · 2020Article
- Evolution of Human Brain Size-Associated NOTCH2NL Genes Proceeds toward Reduced Protein Levels.Molecular biology and evolution · 2020Article
- Notch as an Immunologic Basis of Cancer Disparities.Cancer health disparities · 2019Article
- Human-Specific NOTCH2NL Genes Expand Cortical Neurogenesis through Delta/Notch Regulation.Cell · 2018Article
- Article
- Serine Proteases Enhance Immunogenic Antigen Presentation on Lung Cancer Cells.Cancer immunology research · 2017Article
- Gene expression differences between psoriasis patients with and without inflammatory arthritis.The Journal of investigative dermatology · 2015Article
- Granule protein processing and regulated secretion in neutrophils.Frontiers in immunology · 2014Review
- Microarray analysis provides new insights into the function of apolipoprotein O in HepG2 cell line.Lipids in health and disease · 2013Article
- Mapping of the disease locus and identification of ADAMTS10 as a candidate gene in a canine model of primary open angle glaucoma.PLoS genetics · 2011Article
- Roles of Pofut1 and O-fucose in mammalian Notch signaling.The Journal of biological chemistry · 2008Article
- Article
- Genetic heterogeneity in severe congenital neutropenia: how many aberrant pathways can kill a neutrophil?Current opinion in allergy and clinical immunology · 2007Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in ELA2, encoding the human serine protease neutrophil elastase, cause cyclic and severe congenital neutropenia, and recent evidence indicates that the mutations alter the membrane trafficking of neutrophil elastase. These disorders feature impaired bone marrow production of neutrophils along with excess monocytes-terminally differentiated lineages corresponding to the two alternative fates of myeloid progenitor cells. We utilized a modified yeast two-hybrid system and identified a new, widely expressed gene, N2N, whose product is homologous to Notch2, that interacts with neutrophil elastase. N2N is a 36-kDa protein distributed throughout the cell and secreted. Its amino-terminal sequence consists of several EGF repeats identical to those of the extracellular region of Notch2, and its carboxyl terminus contains a unique 24-residue domain required for interaction with neutrophil elastase. Neutrophil elastase cleaves N2N within EGF repeats in vitro and in living cells, but the C-terminal domain retards proteolysis. In vitro, N2N represses transcriptional activities of Notch proteins. Disease-causing mutations of neutrophil elastase disrupt the interaction with N2N, impair proteolysis of N2N and Notch2, and interfere with Notch2 signaling, suggesting defective proteolysis of an inhibitory form of Notch as an explanation for the alternate switching of cell fates characteristic of hereditary neutropenia.
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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.