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The Notch Interactome: Complexity in Signaling Circuitry

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Molecular Mechanisms of Notch Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1066))

Abstract

The Notch pathway controls a very broad spectrum of cell fates in metazoans during development, influencing proliferation, differentiation and cell death. Given its central role in normal development and homeostasis, misregulation of Notch signals can lead to various disorders including cancer. How the Notch pathway mediates such pleiotropic and differential effects is of fundamental importance. It is becoming increasingly clear through a number of large-scale genetic and proteomic studies that Notch interacts with a staggeringly large number of other genes and pathways in a context-dependent, complex, and highly regulated network, which determines the ultimate biological outcome. How best to interpret and analyze the continuously increasing wealth of data on Notch interactors remains a challenge. Here we review the current state of genetic and proteomic data related to the Notch interactome.

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Abbreviations

BioPlex:

biophysical interactions of ORFeome-based complexes

CADASIL:

cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

DPiM:

Drosophila protein interaction map

NICD:

Notch intracellular domain

PPI:

protein-protein interaction

T-ALL:

T-cell acute lymphoblastic leukemia

Y2H:

yeast two-hybrid

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Acknowledgements

The authors thank the members of the Artavanis-Tsakonas lab for helpful discussions and comments. This work was supported by NIH grants 5R01CA098402 and 5RO1HG003616 to S.A.-T.

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Authors and Affiliations

  1. Department of Cell Biology, Harvard Medical School, Boston, MA, USA

    Diana M. Ho & Spyros Artavanis-Tsakonas

  2. Neurology Research, Biogen Inc., Cambridge, MA, USA

    K. G. Guruharsha & Spyros Artavanis-Tsakonas

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  1. Diana M. Ho
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  2. K. G. Guruharsha
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Correspondence to Spyros Artavanis-Tsakonas .

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  1. Institute of Biochemistry, University of Giessen, Giessen, Germany

    Tilman Borggrefe

  2. Institute of Biochemistry, University of Giessen, Giessen, Germany

    Benedetto Daniele Giaimo

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Ho, D.M., Guruharsha, K.G., Artavanis-Tsakonas, S. (2018). The Notch Interactome: Complexity in Signaling Circuitry. In: Borggrefe, T., Giaimo, B. (eds) Molecular Mechanisms of Notch Signaling. Advances in Experimental Medicine and Biology, vol 1066. Springer, Cham. https://doi.org/10.1007/978-3-319-89512-3_7

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