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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

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Related Experiment Video

Updated: Jun 23, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

High-throughput screening compatible cell-based assay for interrogating activated notch signaling.

Michael K Hancock1, Leisha Kopp, Kun Bi

  • 1Invitrogen Corporation, Madison, Wisconsin 53719, USA.

Assay and Drug Development Technologies
|April 23, 2009
PubMed
Summary
This summary is machine-generated.

Aberrant Notch signaling is implicated in diseases, so we developed a cell-based assay to screen for pathway modulators. This assay identified novel compounds affecting Notch intracellular domain (NICD) signaling, including PI3K/AKT pathway involvement.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Pharmacology

Background:

  • Aberrant Notch pathway signaling is linked to developmental disorders, cancers, and neurodegenerative diseases.
  • Modulating Notch signaling presents a therapeutic strategy for various diseases.
  • The Notch pathway involves ligand binding, receptor cleavage, and nuclear translocation of Notch intracellular domain (NICD) to activate transcription.

Purpose of the Study:

  • To develop and validate a cell-based assay for screening modulators of Notch intracellular domain (NICD) signaling.
  • To identify novel compounds that can modulate NICD signaling.
  • To investigate the role of the PI3K/AKT pathway in regulating NICD signaling.

Main Methods:

  • Engineered HeLa cells with a Notch response element driving beta-lactamase (BLA) reporter gene expression.
  • Utilized a tetracycline-inducible NICD expression system for controlled pathway activation.
  • Screened 19 known compounds and employed RNA interference to validate modulators.

Main Results:

  • The cell-based assay demonstrated a sensitive, quantitative readout for NICD signaling.
  • Identified novel modulators of NICD signaling, including Wnt inhibitor ICG-001 which antagonized signaling.
  • Histone deacetylase, HSP90, and PI3K/mTOR inhibitors (SAHA, 17-AAG, PI-103) activated NICD signaling.
  • AKT and PI3K inhibitors (triciribine, GDC-0941) enhanced reporter activity, implicating the PI3K/AKT pathway.

Conclusions:

  • The developed cell-based assay is suitable for high-throughput screening of NICD pathway modulators.
  • The PI3K/AKT pathway plays a significant role in regulating NICD signaling.
  • This system facilitates the discovery of potential therapeutic agents targeting the Notch pathway.