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Curr Opin Genet Dev. 2008 Oct;18(5):449-54. doi: 10.1016/j.gde.2008.07.013. Epub 2008 Sep 4.

Modulating Notch signaling by pathway-intrinsic and pathway-extrinsic mechanisms.

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Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, von Eulers väg 3, SE-171 77 Stockholm, Sweden.


Despite a relatively simple core-signaling transduction machinery, Notch signaling controls cell differentiation in many different tissues and at multiple stages in a given cell lineage. To understand how Notch generates this multitude of cellular responses, it is important to learn how the Notch-signaling output is modulated at various levels. Pathway-intrinsic as well as pathway-extrinsic mechanisms, including cross-talk between Notch and other major signaling mechanisms, modulate Notch signaling, contributing to the versatile output. In this review, we discuss how Notch signaling is altered in tumors and illustrate the complexity in signaling pathway cross-talk with examples of how Notch synergizes with NF-kappaB signaling and the cellular response to lowered oxygen (hypoxia).

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