The Role of Intracellular Trafficking of Notch Receptors in Ligand-Independent Notch Activation

J. Hounjet, M. Vooijs*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

3 Citations (Web of Science)

Abstract

Aberrant Notch signaling has been found in a broad range of human malignancies. Consequently, small molecule inhibitors and antibodies targeting Notch signaling in human cancers have been developed and tested; however, these have failed due to limited anti-tumor efficacy because of dose-limiting toxicities in normal tissues. Therefore, there is an unmet need to discover novel regulators of malignant Notch signaling, which do not affect Notch signaling in healthy tissues. This review provides a comprehensive overview of the current knowledge on the role of intracellular trafficking in ligand-independent Notch receptor activation, the possible mechanisms involved, and possible therapeutic opportunities for inhibitors of intracellular trafficking in Notch targeting.
Original languageEnglish
Article number1369
Number of pages23
JournalBiomolecules
Volume11
Issue number9
DOIs
Publication statusPublished - 1 Sep 2021

Keywords

  • Drosophila
  • Notch signaling
  • intracellular trafficking
  • ligand-independent
  • mammals
  • therapeutic targeting
  • GAMMA-SECRETASE INHIBITOR
  • PROTEOLYTIC ACTIVATION
  • TRANSMEMBRANE DOMAIN
  • AMYLOID PRECURSOR PROTEIN
  • ENDOCYTIC TRAFFICKING
  • ENDOSOMAL TRAFFICKING
  • DEPENDENT CLEAVAGE
  • RETROGRADE TRANSPORT
  • REGULATORY REGION
  • DROSOPHILA DELTEX

Cite this