ArticleBiochimica et biophysica acta2011
Bimodal regulation of FoxO3 by AKT and 14-3-3.
Article in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 112 citations in OpenAlex.
- The dual role of the PI3K/AKT/mTOR axis in glial cell survival and neuroinflammation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- In vivo evidence for FOXO3-mediated suppression of primordial follicle activation in chickens.Poultry science · 2026Article
- Construction of biomimetic gradient-structured cartilage organoids and mechanistic study of their application for cartilage rejuvenation.Bioactive materials · 2026Article
- Exploring 14-3-3ζ: insights into its role in cancer mechanisms and future therapeutic applications.Hereditas · 2026Review
- Distinct signaling mechanisms and proteome phenotypes are elicited by compartment-specific genetic defects of copper homeostasis.bioRxiv : the preprint server for biology · 2026Article
- BMSC-derived extracellular vesicles affect gluconeogenesis and lipogenesis by releasing 5'-tRF-GlyCCC to improve MAFLD insulin sensitivity.Cell biology and toxicology · 2026Article
- Eupatilin modulates the Mcl-1 ubiquitination status and PI3K/Akt/Foxo3a pathway to inhibit apoptosis and alleviate sepsis-induced acute myocardial injury.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- SIRT2 attenuates stress-induced skeletal muscle atrophy by inhibiting glucocorticoid receptor signalling.bioRxiv : the preprint server for biology · 2025Article
- FoxO1 signaling in B cell malignancies and its therapeutic targeting.FEBS letters · 2025Review
- Integrated transcriptomics and metabolomics studies reveal the therapeutic effects of Astragalus polysaccharides on cancer cachexia muscle atrophy.Scientific reports · 2025Article
- Article
- Recycle, repair, recover: the role of autophagy in modulating skeletal muscle repair and post-exercise recovery.Bioscience reports · 2025Review
- MicroRNAs-associated with FOXO3 in cellular senescence and other stress responses.Biogerontology · 2024Review
- Arsenic disrupts extracellular vesicle-mediated signaling in regenerating myofibers.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Human cytomegalovirus attenuates AKT activity by destabilizing insulin receptor substrate proteins.bioRxiv : the preprint server for biology · 2023Article
- Human 14-3-3 Proteins Site-selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating its Phosphoregulation.Journal of molecular biology · 2023Article
- Towards the Identification of Biomarkers for Muscle Function Improvement in Myotonic Dystrophy Type 1.Journal of neuromuscular diseases · 2023Review
- FoxO1 as a tissue-specific therapeutic target for type 2 diabetes.Frontiers in endocrinology · 2023Review
- Preventive effects of the butanol fraction ofHeliyon · 2022Article
- The Akt Forkhead Box O Transcription Factor Axis Regulates Human Cytomegalovirus Replication.mBio · 2022Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
FoxO3 is a member of FoxO family transcription factors that mediate cellular functions downstream of AKT. FoxO3 phosphorylation by AKT generates binding sites for 14-3-3, which in-turn regulates FoxO3 transcriptional activity and localization. We examine here the functional significance of AKT-FoxO3 interaction and further detail the mechanistic aspects of FoxO3 regulation by AKT and 14-3-3. Our data show that AKT overexpression increases the steady-state levels of FoxO3 protein in a manner dependent on AKT activity and its ability to bind FoxO3. Characterization of the AKT-FoxO3 interaction shows that the three AKT phosphorylation-site-recognition motifs (RxRxxS/T) present on FoxO3, which are required for FoxO3 phosphorylation, are dispensable for AKT binding, suggesting that AKT has a docking point on FoxO3 distinct from the phosphorylation-recognition motifs. Development of a FoxO3 mutant deficient in 14-3-3 binding (P34A), which can be phosphorylated by AKT, established that 14-3-3 binding and not AKT phosphorylation per se controls FoxO3 transcriptional activity. Intriguingly, 14-3-3 binding was found to stabilize FoxO3 by inhibiting its dephosphorylation and degradation rates. Collectively, our data support a model where both AKT and 14-3-3 positively regulate FoxO3 in addition to their established negative roles and that 14-3-3 availability could dictate the fate of phosphorylated FoxO3 toward degradation or recycling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.