ArticleInternational journal of biological sciences2024
FOXO1-mediated nuclear sequestration of STAT3 and AKT1 triggers FOXO3-dependent autophagic death in hypoxic granulosa cells.
Article in International journal of biological sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- PDE4D-CXCL13 axis in gland epithelial cells promotes B cell infiltration in primary Sjögren's syndrome.Acta pharmacologica Sinica · 2026Article
- The ubiquitin-like protein FAT10 enhances the autophagy-mediated degradation of ZO-1 by stabilizing ATG3 to promote the lung metastasis of colon cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Exploring the Reproductive Toxicity of Bisphenol S Through a Network Toxicology and Molecular Docking Analysis.Pediatric discovery · 2026Article
- DNA methylation-mediated regulation of hypoxia-responsive genes facilitates high-altitude adaptation in Tibetan chickens.Poultry science · 2026Article
- Dysregulated post‑translational modifications in granulosa cells drive ovarian dysfunction and potential infertility applications (Review).International journal of molecular medicine · 2026Review
- A novel traditional Chinese medicine compound alleviates broiler ascites syndrome by modulating the IL-6/STAT3/FOXO3a signaling pathway.Poultry science · 2026Article
- Impaired Autophagic Flux in Adipose Tissue Aggravates Pancreatic Injury in Obesity-Related Severe Acute Pancreatitis.Immunity, inflammation and disease · 2026Article
- Molecular Responses of Cold Stress Adaptation in the Red Grouper (Epinephelus Akaara): Compensatory Regulation Between FOXO and MAPK Signaling Pathways.Marine biotechnology (New York, N.Y.) · 2026Article
- Research progress on the mechanism of FOXO protein in sepsis.Apoptosis : an international journal on programmed cell death · 2026Review
- Hypoxia-induced degradation of FTO promotes apoptosis by unmasking RACK1-mediated activation of MTK1-JNK1/2 pathway.Journal of advanced research · 2025Article
- Autophagy in ovary: protective roles, pathological consequences, and unresolved issues.Journal of ovarian research · 2025Review
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Authors and funding
8 authors.
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Abstract
FOXO proteins, especially FOXO1 and FOXO3, are recognized for their roles in controlling apoptosis and autophagy. Both apoptosis and autophagy have been induced in granulosa cells (GCs) by hypoxic conditions in ovarian follicles; however, the exact contribution of FOXO proteins and autophagy to the regulation of GCs apoptosis under hypoxia remains unclear. In this investigation of porcine GCs, we reveal that FOXO1 promotes apoptosis in response to hypoxia through FOXO3-dependent autophagy. We describe how mechanistically, FOXO1 forms a complex with the transcription factor STAT3 during hypoxia. Guided by FOXO1, this complex undergoes nuclear translocation and effectively attaches to the STAT3-responsive element (SRE) located in the FOXO3 promoter region, thereby enhancing the transcriptional expression of FOXO3. Simultaneously, FOXO1 associates with AKT1, thus facilitating its nuclear entry and subsequently reducing the Ser253 phosphorylation of FOXO3, leading to FOXO3 detachment from 14-3-3 and promoting FOXO3 translocation into the nucleus. FOXO3 subsequently stimulates the upregulation of ATG3, ultimately initiating autophagy and autophagy-dependent apoptosis. Our results suggest that hypoxia acts through FOXO1 to induce autophagic death in porcine GCs by promoting the expression and nuclear import of FOXO3.
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