The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Metalloprotease ADAM10 Is Required for Notch1 Site 2 Cleavage
Open accessAbstract
Notch signaling is controlled by ligand binding, which unfolds a negative control region to induce proteolytic cleavage of the receptor. First, a membrane-proximal cleavage is executed by a metalloprotease, removing the extracellular domain. This allows gamma-secretase to execute a second cleavage within the Notch transmembrane domain, which releases the intracellular domain to enter the nucleus. Here we show that the ADAM10 metalloprotease Kuzbanian, but not ADAM17/tumor necrosis factor alpha-converting enzyme, plays an essential role in executing ligand-induced extracellular cleavage at site 2 (S2) in cells and localizes this step to the plasma membrane. Importantly, genetic or pharmacological inhibition of metalloproteases still allowed extracellular cleavage of Notch, indicating the presence of unknown proteases with the ability to cleave at S2. Gain of function mutations identified in human cancers and in model organisms that map to the negative control region alleviate the requirement for ligand binding for extracellular cleavage to occur. Because cancer-causing Notch1 mutations also depend on (rate-limiting) S2 proteolysis, the identity of these alternative proteases has important implications for understanding Notch activation in normal and cancer cells.
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A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells
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Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain
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Self-citationAn Essential Role for Ectodomain Shedding in Mammalian Development
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Self-citationSignalling downstream of activated mammalian Notch
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Self-citationCloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-α
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A Novel Proteolytic Cleavage Involved in Notch Signaling
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Cited by
Bray, S. J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.94 · Cited by 1,012
Notch signaling: simplicity in design, versatility in function
Andersson, E. R., Sandberg, R., & Lendahl, U. (2011) · Development · doi:10.1242/dev.063610 · Cited by 950
The Varied Roles of Notch in Cancer
Aster, J. C., Pear, W. S., & Blacklow, S. C. (2017) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-052016-100127 · Cited by 710
Kuhn, P., Wang, H., Dislich, B., Colombo, A., Zeitschel, U., Ellwart, J. W., Kremmer, E., Roßner, S., & Lichtenthaler, S. F. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.167 · Cited by 621
Metalloproteinases and their natural inhibitors in inflammation and immunity
Khokha, R., Murthy, A., & Weiss, A. (2013) · Nature reviews. Immunology · doi:10.1038/nri3499 · Cited by 552
Metadata
- Authors
- van Tetering, G., van Diest, P., Verlaan, I., van der Wall, E., Kopan, R., & Vooijs, M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 284
- Issue
- 45
- Pages
- 31018-31027
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1969414295
- Cited by
- 274
- References
- 57
- FWCI
- 8.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Metalloprotease ADAM10 Is Required for Notch1 Site 2 Cleavage. https://app.cochat.ai/papers/10.1074/jbc.m109.006775
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- van Tetering, G., van Diest, P., Verlaan, I., van der Wall, E., Kopan, R., & Vooijs, M. (2009). Metalloprotease ADAM10 Is Required for Notch1 Site 2 Cleavage. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m109.006775
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
