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Updated: Jul 9, 2025

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

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Comprehensive analysis of the proximity-dependent nuclear interactome for the oncoprotein NOTCH1 in live cells

Haydee M Torres1, Fang Fang2, Danielle G May3

  • 1Cancer Biology & Immunotherapies Group, Sanford Research, Sioux Falls, South Dakota, USA; Department of Chemistry and Biochemistry, South Dakota State University, Brookings, South Dakota, USA.

The Journal of Biological Chemistry
|December 3, 2023
PubMed

Insights

Researchers explored the nuclear interactions of the Notch1 oncoprotein using proximity-dependent biotin identification. This study reveals novel protein associations critical for understanding Notch signaling in cancer and identifying new therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Signaling

Background:

  • Notch signaling is crucial for cell fate determination and is implicated in various human cancers due to mutations in NOTCH1.
  • Targeting Notch signaling is a promising strategy for cancer treatment.
  • The nuclear protein interactions of the Notch1 oncoprotein are not well understood.

Purpose of the Study:

  • To identify in vivo protein associations with the nuclear Notch1 intracellular domain in live cells.
  • To uncover the mechanisms regulating Notch signaling in tumorigenesis.
  • To identify potential therapeutic targets for Notch-addicted tumors.

Main Methods:

  • Proximity-dependent biotin identification (BioID) was employed to map protein interactions.
  • Protein network analysis, proximity-based ligation, in vivo cross-linking, and coimmunoprecipitation assays were used for validation.
  • Data mining was performed to identify potential drug targets.

Main Results:

  • A comprehensive list of proteins interacting with the Notch1 intracellular domain was identified, including transcription factors, DNA repair/replication factors, and chromatin remodelers (NuRD, SWI/SNF).
  • Interactions with protein modifiers like USP7 and components of other signaling pathways were discovered.
  • Validation confirmed interactions with histone deacetylase 1 and GATAD2B in cancer cell lines.

Conclusions:

  • This study provides a valuable resource for understanding Notch1's nuclear interactome.
  • The findings offer insights into the regulation of Notch signaling in cancer.
  • Potential drug targets for inhibiting Notch signaling in Notch-addicted tumors were revealed.
Keywords:
BioIDHDAC1NICDNOTCH1Notch pathwayProteomicscancernetwork analysisprotein-protein interaction

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