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Updated: Feb 16, 2026
Enhanced Yeast One-hybrid Screens To Identify Transcription Factor Binding To Human DNA Sequences
Published on: February 11, 2019
A high-content screen identifies inhibitors of nuclear export of forkhead transcription factors
David C Bouck1, Peter Shu, Jimmy Cui
1Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Abstract:
Class O forkhead box (FOXO) transcription factors are downstream targets of the PI3K/AKT signaling pathway, which is upregulated in many tumors. AKT phosphorylates and inactivates FOXO1 by relocating it to the cytoplasm. Because FOXO1 functions as a tumor suppressor by negatively regulating cell cycle progression and cell survival, compounds that promote FOXO1 localization to the nucleus might have therapeutic value in oncology. Here the authors describe the identification of such compounds by using an image-based, high-content screen. Compounds that were active in retaining FOXO1 in the nucleus were tested to determine their pathway specificity and isoform specificity by using high-content assays for Rev and FOXO3, respectively.
Insights
Researchers identified compounds that promote FOXO1 nuclear localization, a potential cancer therapy. These compounds could counteract the PI3K/AKT pathway
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- The PI3K/AKT signaling pathway is often upregulated in tumors.
- Class O forkhead box (FOXO) transcription factors, including FOXO1, are downstream targets of this pathway.
- AKT phosphorylates and inactivates FOXO1, causing its relocation to the cytoplasm, which promotes tumor growth.
Purpose of the Study:
- To identify compounds that promote FOXO1 nuclear localization.
- To explore therapeutic strategies for oncology by targeting FOXO1.
Main Methods:
- An image-based, high-content screening approach was employed.
- Compounds retaining FOXO1 in the nucleus were identified.
- Pathway and isoform specificity were assessed using high-content assays for Rev and FOXO3.
Main Results:
- Novel compounds were identified that retain FOXO1 in the nucleus.
- The identified compounds' effects on pathway and FOXO isoforms were characterized.
Conclusions:
- Compounds promoting FOXO1 nuclear localization may hold therapeutic potential in cancer treatment.
- Targeting FOXO1 presents a promising strategy for oncological interventions.
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