ArticlePloS one2015
O-fucosylation of DLL3 is required for its function during somitogenesis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07243470 (A Multicenter, Open-label Phase I/II Trial Aiming to Assess the Safety and Clinical Activity of Tarlatamab in Combination With Metronomic Temozolomide in Adolescents and Adults' Patients With High Grade Brain Tumors), which is not on this map. Cited by 31 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.
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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.
A Multicenter, Open-label Phase I/II Trial Aiming to Assess the Safety and Clinical Activity of Tarlatamab in Combination With Metronomic Temozolomide in Adolescents and Adults' Patients With High Grade Brain Tumors
Who cites it
31 citing papers in PubMed, 60 citations in OpenAlex.
- A Splice Acceptor Variant inGenes · 2026Article
- ProteinMolecules (Basel, Switzerland) · 2025Review
- Article
- DLL3 regulates Notch signaling in small cell lung cancer.iScience · 2022Article
- Lfng and Dll3 cooperate to modulate protein interactions in cis and coordinate oscillatory Notch pathway activation in the segmentation clock.Developmental biology · 2022Article
- Glycans that regulate Notch signaling in the intestine.Biochemical Society transactions · 2022Review
- Biophysics of Notch Signaling.Annual review of biophysics · 2021Review
- Current Views on the Roles ofBiomolecules · 2021Review
- Multifaceted regulation of Notch signaling by glycosylation.Glycobiology · 2021Review
- Cell-Type-Specific Gene Expression in Developing Mouse Neocortex: Intermediate Progenitors Implicated in Axon Development.Frontiers in molecular neuroscience · 2021Article
- Article
- POFUT1 is dispensable for structure, function and survival of mouse podocytes.American journal of translational research · 2020Article
- The Role of DLLs in Cancer: A Novel Therapeutic Target.OncoTargets and therapy · 2020Review
- Decoding the PTM-switchboard of Notch.Biochimica et biophysica acta. Molecular cell research · 2019Review
- Protein O-fucosylation: structure and function.Current opinion in structural biology · 2019Review
- Identification of novel LFNG mutations in spondylocostal dysostosis.Journal of human genetics · 2019Article
- Cell Surface Notch Ligand DLL3 is a Therapeutic Target in Isocitrate Dehydrogenase-mutant Glioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Multiple roles for O-glycans in Notch signalling.FEBS letters · 2018Review
- Congenital diseases caused by defectiveNagoya journal of medical science · 2018Review
- Notch Ligand Binding Assay Using Flow Cytometry.Bio-protocol · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Delta-like 3 (DLL3) is a member of the DSL family of Notch ligands in amniotes. In contrast to DLL1 and DLL4, the other Delta-like proteins in the mouse, DLL3 does not bind in trans to Notch and does not activate the receptor, but shows cis-interaction and cis-inhibitory properties on Notch signaling in vitro. Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. Like LFNG, DLL3 is located within the trans-Golgi, however, its biochemical function is still unclear. Here, we show that i) both proteins interact, ii) epidermal growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites for POFUT1, and iii) further modified by FNG proteins in vitro. Embryos double homozygous for null mutations in Dll3 and Lfng are phenotypically indistinguishable from the single mutants supporting a potential common function. Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. However, in contrast to wild type DLL3, O-fucosylation-deficient DLL3 cannot compensate for the loss of endogenous DLL3 during somitogenesis in the embryo. Together our results suggest that the cis-inhibitory activity of DLL3 observed in cultured cells might not fully reflect its assumed essential physiological property, suggest that DLL3 and LFNG act together, and strongly supports that modification of DLL3 by O-linked fucose is essential for its function during somitogenesis.
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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.