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Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain.

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  • 1. Division of Dermatology, Department of Molecular Biology and Pharmacology, Washington University, St. Louis, MO 63110, USA.
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    • Kopan R 1
    (1 author)

ORCIDs linked to this article

Proceedings of the National Academy of Sciences of the United States of America, 01 Feb 1996, 93(4):1683-1688
https://doi.org/10.1073/pnas.93.4.1683 PMID: 8643690 PMCID: PMC40002

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Abstract 

Previous studies imply that the intracellular domain of Notch1 must translocate to the nucleus for its activity. In this study, we demonstrate that a mNotch1 mutant protein that lacks its extracellular domain but retains its membrane-spanning region becomes proteolytically processed on its intracellular surface and, as a result, the activated intracellular domain (mNotchIC) is released and can move to the nucleus. Proteolytic cleavage at an intracellular site is blocked by protease inhibitors. Intracellular cleavage is not seen in cells transfected with an inactive variant, which includes the extracellular lin-Notch-glp repeats. Collectively, the studies presented here support the model that mNotch1 is proteolytically processed and the cleavage product is translocated to the nucleus for mNotch1 signal transduction.

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Proc Natl Acad Sci U S A. 1996 Feb 20; 93(4): 1683–1688.
PMCID: PMC40002
PMID: 8643690

Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain.

R Kopan, E H Schroeter, H Weintraub, and J S Nye
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Abstract

Previous studies imply that the intracellular domain of Notch1 must translocate to the nucleus for its activity. In this study, we demonstrate that a mNotch1 mutant protein that lacks its extracellular domain but retains its membrane-spanning region becomes proteolytically processed on its intracellular surface and, as a result, the activated intracellular domain (mNotchIC) is released and can move to the nucleus. Proteolytic cleavage at an intracellular site is blocked by protease inhibitors. Intracellular cleavage is not seen in cells transfected with an inactive variant, which includes the extracellular lin-Notch-glp repeats. Collectively, the studies presented here support the model that mNotch1 is proteolytically processed and the cleavage product is translocated to the nucleus for mNotch1 signal transduction.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
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