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Notch Signaling Pathway

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...

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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: Mar 22, 2026

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Published on: February 21, 2018

PRDM14 promotes RAG-dependent Notch1 driver mutations in mouse T-ALL.

Brandi L Carofino¹, Bernard Ayanga², Lauren J Tracey³

¹Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, 77030 USA Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030 USA.

|April 24, 2016

Summary

The epigenetic regulator PRDM14 drives T-cell acute lymphoblastic leukemia (T-ALL) by activating NOTCH1 through RAG-dependent DNA deletions. This mechanism hijacks cellular machinery, promoting cancer development.

Keywords:

Driver mutation NOTCH1 PRDM14 RAG recombination T-cell acute lymphoblastic leukemia

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Published on: June 9, 2023

Area of Science:

Epigenetics
Hematopoiesis
Cancer Biology

Background:

PRDM14 maintains stem cell identity and germ cell potency.
Supraphysiological PRDM14 in hematopoietic cells causes rapid T-cell acute lymphoblastic leukemia (T-ALL) in mice.

Purpose of the Study:

Investigate the mechanism of PRDM14-induced T-ALL.
Identify the role of NOTCH1 in this leukemia model.

Main Methods:

Utilized a PRDM14-FLAG mouse model.
Analyzed RAG-dependent promoter deletions and epigenetic changes (H3K4me1/3).
Assessed the impact of RAG deficiency on T-ALL development.

Main Results:

PRDM14-induced T-ALLs are driven by NOTCH1 activation.
NOTCH1 activation occurs via RAG-dependent deletions creating truncated proteins.
PRDM14 binding at the NOTCH1 locus creates a permissive epigenetic state for RAG access.
RAG deficiency prevents T-ALL development and NOTCH1 deletions.

Conclusions:

PRDM14 expands progenitor cells and creates a permissive epigenetic environment for oncogenic mutations.
Cancer develops through the misuse of endogenous DNA recombination machinery, specifically targeting NOTCH1.