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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

6.7K
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...
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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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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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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Related Experiment Video

Updated: Feb 22, 2026

Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
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Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis

Published on: December 12, 2019

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A sweet development in Notch regulation.

Hans Bakker1, Rita Gerardy-Schahn2

  • 1From the Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.

The Journal of Biological Chemistry
|September 24, 2017
PubMed
Summary
This summary is machine-generated.

Glycosylation of the Notch protein impacts its stability. While O-fucose and O-glucose stabilize EGF repeats, xylose addition weakens them by altering glycan binding.

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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
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Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
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Area of Science:

  • Biochemistry
  • Glycobiology
  • Developmental Biology

Background:

  • The Notch signaling pathway is essential for embryonic development and cell fate determination.
  • Notch proteins possess numerous extracellular Epidermal Growth Factor-like (EGF) domains.
  • These EGF domains undergo complex and variable glycosylation.

Purpose of the Study:

  • To investigate the distinct effects of different glycosylation patterns on the stability and structure of Notch EGF repeats.
  • To elucidate the molecular mechanisms by which specific glycans influence protein conformation.

Main Methods:

  • Analysis of glycosylation patterns on Notch EGF domains.
  • Biochemical assays to assess protein stability under different glycosylation conditions.
  • Structural analysis to understand glycan-protein interactions.

Main Results:

  • O-fucose and O-glucose modifications were found to stabilize the Notch EGF repeats.
  • Extension of O-glucose with xylose resulted in decreased stability of the EGF repeats.
  • The weakening of stability by xylose-extended glycans is attributed to their binding within a specific protein groove.

Conclusions:

  • Glycosylation plays a critical role in modulating the structural integrity of Notch EGF domains.
  • Specific glycan structures, such as O-fucose and O-glucose, enhance protein stability.
  • The position and composition of glycans, like xylose addition, can destabilize protein structure by altering binding interactions.