ArticleThe Journal of biological chemistry2007
Proteolytic processing of delta-like 1 by ADAM proteases.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 126 citations in OpenAlex.
- Expression ofInternational journal of molecular sciences · 2026Article
- ADAM9: an updated view of its biology and pathology.Molecular biology reports · 2026Review
- ADAM9 in tumor biology: molecular functions, clinical implications, and therapeutic targeting.Cellular & molecular biology letters · 2026Review
- Contributions of ADAM12 via HB-EGF/EGFR signaling cascades to EMT and cancer progression in pancreas.Molecular and clinical oncology · 2026Article
- The role of ADAM8 in intrahepatic cholangiocarcinoma.Discover oncology · 2025Review
- Soluble DLL1 as an Indicator of acute kidney injury and postoperative delirium following cardiac surgery: a secondary analysis of a prospective study.Perioperative medicine (London, England) · 2025Article
- Human Myobundle Platform for Studying the Role of Notch Signaling in Satellite Cell Phenotype and Function.Advanced healthcare materials · 2025Article
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- ADAM10 and ADAM17, Major Regulators of Chronic Kidney Disease Induced Atherosclerosis?International journal of molecular sciences · 2023Review
- A Disintegrin and Metalloproteinase 10 (ADAM10) Is Essential for Oligodendrocyte Precursor Development and Myelination in the Mouse Brain.Molecular neurobiology · 2023Article
- ADAM12 abrogation alters immune cell infiltration and improves response to checkpoint blockade therapy in the T11 murine model of triple-negative breast cancer.Oncoimmunology · 2023Article
- Cleaved Delta like 1 intracellular domain regulates neural development via Notch signal-dependent and -independent pathways.Development (Cambridge, England) · 2021Article
- Contribution of ADAM17 and related ADAMs in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2021Review
- ADAM and ADAMTS Proteins, New Players in the Regulation of Hepatocellular Carcinoma Microenvironment.Cancers · 2021Review
- MALAT1: A Pivotal lncRNA in the Phenotypic Switch of Gastric Smooth Muscle CellsFrontiers in pharmacology · 2021Article
- Structure, regulatory factors and cancer-related physiological effects of ADAM9.Cell adhesion & migration · 2020Review
- Delta-like Canonical Notch Ligand 1 in Patients Following Liver Transplantation-A Secondary Analysis of a Prospective Cohort Study.Diagnostics (Basel, Switzerland) · 2020Article
- An Overview of ADAM9: Structure, Activation, and Regulation in Human Diseases.International journal of molecular sciences · 2020Review
- Extracellular matrix dynamics in vascular remodeling.American journal of physiology. Cell physiology · 2020Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Delta-like 1 (Dll1) is a mammalian ligand for Notch receptors. Interactions between Dll1 and Notch in trans activate the Notch pathway, whereas Dll1 binding to Notch in cis inhibits Notch signaling. Dll1 undergoes proteolytic processing in its extracellular domain by ADAM10. In this work we demonstrate that Dll1 represents a substrate for several other members of the ADAM family. In co-transfected cells, Dll1 is constitutively cleaved by ADAM12, and the N-terminal fragment of Dll1 is released to medium. ADAM12-mediated cleavage of Dll1 is cell density-dependent, takes place in cis orientation, and does not require the presence of the cytoplasmic domain of ADAM12. Full-length Dll1, but not its N- or C-terminal proteolytic fragment, co-immunoprecipitates with ADAM12. By using a Notch reporter construct, we show that Dll1 processing by ADAM12 increases Notch signaling in a cell-autonomous manner. Furthermore, ADAM9 and ADAM17 have the ability to process Dll1. In contrast, ADAM15 does not cleave Dll1, although the two proteins still co-immunoprecipitate with each other. Asn-353 present in the catalytic motif of ADAM12 and other Dll1-processing ADAMs, but absent in ADAM15, is necessary for Dll1 cleavage. Dll1 cleavage is reduced in ADAM9/12/15(-/-) mouse embryonic fibroblasts (MEFs), suggesting that the endogenous ADAM9 and/or ADAM12 present in wild type MEFs contribute to Dll1 processing. Finally, the endogenous Dll1 present in primary mouse myoblasts undergoes cleavage in confluent, differentiating myoblast cultures, and this cleavage is decreased by ADAM12 small interfering RNAs. Our findings expand the role of ADAM proteins in the regulation of Notch signaling.
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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.