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Updated: Jun 2, 2026
05:48
Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
Published on: January 2, 2018
Role of STRAP in regulating GSK3β function and Notch3 stabilization
Nilesh D Kashikar1, Wanguang Zhang, Pierre P Massion
1Vanderbilt University School of Medicine, Nashville, TN USA.
Cell Cycle (Georgetown, Tex.)
|April 20, 2011
Summary
The scaffold protein STRAP binds Glycogen synthase kinase 3β (GSK3β) and stabilizes Notch3, a protein implicated in non-small cell lung cancer. STRAP
Area of Science:
- Cellular signaling pathways
- Protein-protein interactions
- Cancer biology
Background:
- Glycogen synthase kinase 3β (GSK3β) regulates cellular processes by phosphorylating substrates.
- The recruitment mechanisms for many GSK3β substrates remain unclear.
- Notch signaling is implicated in various cancers, including non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To elucidate the interaction between GSK3β and its novel scaffold protein, STRAP.
- To investigate the role of STRAP in the regulation of Notch3 stability and function.
- To explore the potential oncogenic role of STRAP in non-small cell lung cancer.
Main Methods:
- Co-immunoprecipitation assays to establish protein binding.
- Use of small-molecule inhibitors to probe protein interactions.
- In vivo ubiquitination assays to assess protein stability.
- Immunohistochemical staining of tissue microarrays for co-localization studies.
Main Results:
- STRAP binds to GSK3β via its WD40 domains, forming a ternary complex with GSK3β and Axin.
- STRAP binds to the intracellular fragment of Notch3 (ICN3) through its ankyrin repeat region.
- STRAP reduces ICN3 ubiquitination, leading to ICN3 stabilization.
- STRAP and Notch3 are co-upregulated and co-localized in a significant proportion of NSCLC tissues.
Conclusions:
- STRAP acts as a scaffold protein that modulates GSK3β activity towards Notch3.
- STRAP stabilizes ICN3, potentially contributing to its oncogenic functions in NSCLC.
- The findings reveal a novel regulatory mechanism for Notch3 and highlight STRAP as a potential therapeutic target in NSCLC.
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