The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Selective Use of ADAM10 and ADAM17 in Activation of Notch1 Signaling
Open accessAbstract
Notch signaling requires a series of proteolytic cleavage events to release the Notch intracellular domain (NICD) that functions directly in signal transduction. The Notch receptor is locked down in a protease-resistant state by a negative regulatory region (NRR) that protects an ADAM (a disintegrin and metalloprotease) cleavage site. Engagement with ligand-bearing cells induces global conformational movements in Notch that unfold the NRR structure to expose the ADAM cleavage site and initiate proteolytic activation. Although both ADAM10 and ADAM17 have been reported to cleave Notch to facilitate NICD release by gamma-secretase, the relevant ADAM has remained controversial. Our study provides new insight into this conflict, as we find that although Notch1 (N1) is a substrate for both ADAM10 and ADAM17, the particular ADAM required for receptor activation is context dependent. Specifically, ADAM10 was absolutely required for N1 signaling induced by ligands, while signaling independent of ligands required ADAM17. In contrast to the strict and differential use of ADAM10 and ADAM17 in normal and dysregulated signaling, respectively, both proteases participated in signaling intrinsic to N1 mutations associated with leukemia. We propose that in addition to exposing the ADAM cleavage site, activating N1 conformational changes facilitate selective cleavage by specific proteases.
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Cites
Notch Signaling: Cell Fate Control and Signal Integration in Development
Artavanis-Tsakonas, S., Rand, M. D., & Lake, R. J. (1999) · Science · doi:10.1126/science.284.5415.770 · Cited by 5,909
Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia
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Notch signalling: a simple pathway becomes complex
Bray, S. J. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2009 · Cited by 2,620
An Essential Role for Ectodomain Shedding in Mammalian Development
Peschon, J. J., Slack, J. L., Reddy, P., Stocking, K. L., Sunnarborg, S. W., Lee, D. C., Russell, W. E., Castner, B. J., Johnson, R. S., Fitzner, J. N., et al. (1998) · Science · doi:10.1126/science.282.5392.1281 · Cited by 1,607
Deficient T Cell Fate Specification in Mice with an Induced Inactivation of Notch1
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HES and HERP families: Multiple effectors of the notch signaling pathway
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A Novel Proteolytic Cleavage Involved in Notch Signaling
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Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands
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Cited by
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
Nowell, C. S., & Radtke, F. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2016.145 · Cited by 369
Metadata
- Authors
- Bozkulak, E. C., & Weinmaster, G.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2009-11-01
- Volume
- 29
- Issue
- 21
- Pages
- 5679-5695
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2129270491
- Cited by
- 309
- References
- 61
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- green
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