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Phosphorylation and Proteolytic Cleavage of Notch in Canonical and Noncanonical Notch Signaling

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Notch Signaling in Embryology and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1227))

Abstract

The Notch signaling pathway seems deceptively simple, with its key feature being a direct connection between extracellular signal and transcriptional output without the need for an extended chain of protein intermediaries as required by so many other signaling paradigms. However, this apparent simplicity hides considerable complexity. Consistent with its central role in many aspects of development, Notch signaling has an extensive collection of mechanisms that it employs alongside of its core transcriptional machinery. These so-called noncanonical Notch pathways diversify the potential outputs of Notch, and allow it to coordinate regulation of many aspects of the biology of cells. Here we will review noncanonical Notch signaling with special attention to the role of posttranslational modifications of Notch. We will also consider the importance of coordinating the activity of gene expression with regulation of cell morphology in biological processes, including axon guidance and other morphological events during embryogenesis.

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Abbreviations

CNS:

Central nervous system

CSL:

CBF/RBP-Jκ in mammals, Su(H) in Drosophila, and Lag-1 in C. elegans

DSL:

Delta, Serrate, LAG-2

NICD:

Notch intracellular domain

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Acknowledgments

E.G. was supported by the Basic Neuroscience Program in the Division of Intramural Research of NINDS, NIH (Z01 NS003013). G.H. was supported by institutional funds from Clarkson University.

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Correspondence to Edward Giniger .

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© 2020 This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply

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Hunter, G.L., Giniger, E. (2020). Phosphorylation and Proteolytic Cleavage of Notch in Canonical and Noncanonical Notch Signaling. In: Reichrath, J., Reichrath, S. (eds) Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine and Biology, vol 1227. Springer, Cham. https://doi.org/10.1007/978-3-030-36422-9_4

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