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Updated: Jun 28, 2026
09:58
Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
Dexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcription
Kwok-Fai Lau1, Wing-Man Chan, Michael S Perkinton
1Department of Biochemistry and Molecular Biotechnology Programme, Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR. kflau@cuhk.edu.hk
The Journal of Biological Chemistry
|October 17, 2008
Summary
Dexras1 suppresses transcription mediated by FE65 and the amyloid precursor protein (APP) intracellular domain. FE65 phosphorylation at tyrosine 547 reduces Dexras1 binding, enhancing this transcription and impacting Tau phosphorylation via GSK3 beta.
Area of Science:
- Molecular Biology
- Cell Signaling
- Neuroscience
Background:
- FE65 is an adaptor protein crucial for transcription involving the amyloid precursor protein (APP) intracellular domain.
- The precise regulatory mechanisms governing FE65-APP-mediated transcription remain incompletely understood.
Purpose of the Study:
- To investigate the role of Dexras1, a small G protein, in regulating FE65-APP-mediated transcription.
- To elucidate the impact of FE65 phosphorylation on its interaction with Dexras1 and subsequent transcriptional activity.
Main Methods:
- Co-immunoprecipitation assays to assess protein-protein interactions between FE65, APP, and Dexras1.
- Reporter gene assays to quantify FE65-APP-mediated transcriptional activity.
- Small interfering RNA (siRNA) knockdown of Dexras1 to evaluate its functional impact.
- Western blotting to analyze protein expression and phosphorylation levels (e.g., Tau).
Main Results:
- Dexras1 binds to the FE65 PTB2 domain and potently suppresses FE65-APP-mediated transcription.
- Dexras1 and APP can bind FE65 simultaneously, indicating suppression is not competitive.
- Phosphorylation of FE65 at tyrosine 547 reduces Dexras1 binding while enhancing FE65-APP transcription.
- Dexras1 inhibits the transcription of glycogen synthase kinase 3beta (GSK3 beta), a target gene.
- Dexras1 knockdown increases GSK3 beta expression and Tau phosphorylation.
Conclusions:
- Dexras1 acts as a suppressor of FE65-APP-mediated transcription.
- FE65 tyrosine 547 phosphorylation enhances transcription by reducing Dexras1 binding.
- This interaction modulates FE65-APP signaling, revealing a novel regulatory mechanism impacting GSK3 beta and Tau phosphorylation.
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