ArticlePLoS pathogens2009
KSHV manipulates Notch signaling by DLL4 and JAG1 to alter cell cycle genes in lymphatic endothelia.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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.
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.
Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
- Article
- Oncogenic Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus on Cell Metabolism and Cell Transformation.Journal of medical virology · 2025Review
- The cellular Notch1 protein promotes KSHV reactivation in an Rta-dependent manner.Journal of virology · 2024Article
- Article
- Onco-Pathogen Mediated Cancer Progression and Associated Signaling Pathways in Cancer Development.Pathogens (Basel, Switzerland) · 2023Review
- Dysregulation of the miR-30c/DLL4 axis by circHIPK3 is essential for KSHV lytic replication.EMBO reports · 2022Article
- Gene expression in meningeal lymphatic endothelial cells following traumatic brain injury in mice.PloS one · 2022Article
- PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment.PLoS pathogens · 2019Article
- Unbiased Screening of Activated Receptor Tyrosine Kinases (RTKs) in Tumor Extracts Using a Mouse Phospho-RTK Array Kit.Bio-protocol · 2019Article
- Genome-Wide Identification of Direct RTA Targets Reveals Key Host Factors for Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation.Journal of virology · 2019Article
- Molecular mechanisms of viral oncogenesis in humans.Nature reviews. Microbiology · 2018Review
- Delta-like ligand 4 in hepatocellular carcinoma intrinsically promotes tumour growth and suppresses hepatitis B virus replication.World journal of gastroenterology · 2018Article
- KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis.PLoS pathogens · 2018Article
- Kaposi sarcoma herpesvirus pathogenesis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- KSHV and the Role of Notch Receptor Dysregulation in Disease Progression.Pathogens (Basel, Switzerland) · 2017Review
- Notch Signaling in Endothelial Cells: Is It the Therapeutic Target for Vascular Neointimal Hyperplasia?International journal of molecular sciences · 2017Review
- microRNAs in the Lymphatic Endothelium: Master Regulators of Lineage Plasticity and Inflammation.Frontiers in immunology · 2017Review
- Fine-Tuning of the Kaposi's Sarcoma-Associated Herpesvirus Life Cycle in Neighboring Cells through the RTA-JAG1-Notch Pathway.PLoS pathogens · 2016Article
- KSHV-Mediated Angiogenesis in Tumor Progression.Viruses · 2016Review
- KSHV Genome Replication and Maintenance.Frontiers in microbiology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Increased expression of Notch signaling pathway components is observed in Kaposi sarcoma (KS) but the mechanism underlying the manipulation of the canonical Notch pathway by the causative agent of KS, Kaposi sarcoma herpesvirus (KSHV), has not been fully elucidated. Here, we describe the mechanism through which KSHV directly modulates the expression of the Notch ligands JAG1 and DLL4 in lymphatic endothelial cells. Expression of KSHV-encoded vFLIP induces JAG1 through an NFkappaB-dependent mechanism, while vGPCR upregulates DLL4 through a mechanism dependent on ERK. Both vFLIP and vGPCR instigate functional Notch signalling through NOTCH4. Gene expression profiling showed that JAG1- or DLL4-stimulated signaling results in the suppression of genes associated with the cell cycle in adjacent lymphatic endothelial cells, indicating a role for Notch signaling in inducing cellular quiescence in these cells. Upregulation of JAG1 and DLL4 by KSHV could therefore alter the expression of cell cycle components in neighbouring uninfected cells during latent and lytic phases of viral infection, influencing cellular quiescence and plasticity. In addition, differences in signaling potency between these ligands suggest a possible complementary role for JAG1 and DLL4 in the context of KS.
Indexed as
Identifiers
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.