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The Notch Interactome: Complexity in Signaling Circuitry

  • Diana M. Ho
  • K. G. Guruharsha
  • Spyros Artavanis-Tsakonas
Chapter
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Genome-wide screens Genetic modifiers Notch signal integration Protein-protein interactions Signaling interactome 

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

Notes

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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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Diana M. Ho
    • 1
  • K. G. Guruharsha
    • 2
  • Spyros Artavanis-Tsakonas
    • 1
    • 2
  1. 1.Department of Cell BiologyHarvard Medical SchoolBostonUSA
  2. 2.Neurology ResearchBiogen Inc.CambridgeUSA

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