The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
The γ-secretase-generated intracellular domain of β-amyloid precursor protein binds Numb and inhibits Notch signaling
Open accessAbstract
The β-amyloid precursor protein (APP) and the Notch receptor undergo intramembranous proteolysis by the Presenilin-dependent γ-secretase. The cleavage of APP by γ-secretase releases amyloid-β peptides, which have been implicated in the pathogenesis of Alzheimer's disease, and the APP intracellular domain (AID), for which the function is not yet well understood. A similar γ-secretase-mediated cleavage of the Notch receptor liberates the Notch intracellular domain (NICD). NICD translocates to the nucleus and activates the transcription of genes that regulate the generation, differentiation, and survival of neuronal cells. Hence, some of the effects of APP signaling and Alzheimer's disease pathology may be mediated by the interaction of APP and Notch. Here, we show that membrane-tethered APP binds to the cytosolic Notch inhibitors Numb and Numb-like in mouse brain lysates. AID also binds Numb and Numb-like, and represses Notch activity when released by APP. Thus, γ-secretase may have opposing effects on Notch signaling; positive by cleaving Notch and generating NICD, and negative by processing APP and generating AID, which inhibits the function of NICD.
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Cites
ALZHEIMER'S DISEASE: Genetic Studies and Transgenic Models
Price, D. L., Tanzi, R. E., Borchelt, D. R., & Sisodia, S. S. (1998) · Annual Review of Genetics · doi:10.1146/annurev.genet.32.1.461 · Cited by 406
Cited by
Rašin, M.-R., Gazula, V.-R., Breunig, J. J., Kwan, K. Y., Johnson, M. B., Liu-Chen, S., Li, H.-S., Jan, L. Y., Jan, Y.-N., Rakic, P., et al. (2007) · Nature Neuroscience · doi:10.1038/nn1924 · Cited by 316
Self-citationMelchor, J. P., Pawlak, R., & Strickland, S. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-26-08867.2003 · Cited by 202
Kim, H.-S., Kim, E.-M., Lee, J.-P., Park, C. H., Kim, S., Seo, J.-H., Chang, K.-A., Yu, E., Jeong, S.-J., Chong, Y. H., et al. (2003) · The FASEB Journal · doi:10.1096/fj.03-0106fje · Cited by 183
The physiology of the β‐amyloid precursor protein intracellular domain AICD
Pardossi‐Piquard, R., & Checler, F. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07475.x · Cited by 159
Curcuminoids enhance memory in an amyloid-infused rat model of Alzheimer’s disease
Ahmed, T., Enam, S. A., & Gilani, A. H. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.05.078 · Cited by 156
Metadata
- Authors
- Roncarati, R., Šestan, N., Scheinfeld, M. H., Berechid, B. E., Lopez, P. A., Meucci, O., McGlade, J. C., Rakic, P., & D'Adamio, L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-05-14
- Volume
- 99
- Issue
- 10
- Pages
- 7102-7107
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1991697476
- Cited by
- 196
- References
- 1
- FWCI
- 10.47
- Type
- journal article
- Language
- en
- Open access
- green
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- Roncarati, R., Šestan, N., Scheinfeld, M. H., Berechid, B. E., Lopez, P. A., Meucci, O., McGlade, J. C., Rakic, P., & D'Adamio, L. (2002). The γ-secretase-generated intracellular domain of β-amyloid precursor protein binds Numb and inhibits Notch signaling. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.102192599
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