ArticleCell cycle (Georgetown, Tex.)2016
Evidence for AKT-independent regulation of FOXO1 and FOXO3 in haematopoietic stem and progenitor cells.
Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- A randomized 3-way crossover study indicates that high-protein feeding induces de novo lipogenesis in healthy humans.JCI insight · 2019Trial
- Lipopeptides modulate lipid metabolism and immune performance in largemouth bass (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- FoxO1 regulates human haematopoietic stem cells self-renewal and engraftment.Molecular biology reports · 2024Article
- Mitochondrial regulation of erythropoiesis in homeostasis and disease.British journal of haematology · 2024Review
- Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024Review
- The FOXO1 inhibitor AS1842856 triggers apoptosis in glioblastoma multiforme and basal-like breast cancer cells.FEBS open bio · 2023Article
- FoxO Transcription Factors: Applicability as a Novel Immune Cell Regulators and Therapeutic Targets in Oxidative Stress-Related Diseases.International journal of molecular sciences · 2022Review
- The Role of Nutrients in Maintaining Hematopoietic Stem Cells and Healthy Hematopoiesis for Life.International journal of molecular sciences · 2022Review
- The Glucocorticoid Receptor Polymorphism Landscape in Patients With Diamond Blackfan Anemia Reveals an Association Between Two Clinically Relevant Single Nucleotide Polymorphisms and Time to Diagnosis.Frontiers in physiology · 2021Article
- Unraveling the Big Sleep: Molecular Aspects of Stem Cell Dormancy and Hibernation.Frontiers in physiology · 2021Review
- NVP-BEZ235 or JAKi Treatment leads to decreased survival of examined GBM and BBC cells.Cancer treatment and research communications · 2021Article
- FOXO activity adaptation safeguards the hematopoietic stem cell compartment in hyperglycemia.Blood advances · 2020Article
- FOXO transcription factors activate alternative major immediate early promoters to induce human cytomegalovirus reactivation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The PI3K pathway impacts stem gene expression in a set of glioblastoma cell lines.Journal of cancer research and clinical oncology · 2020Article
- Control of Immediate Early Gene Expression for Human Cytomegalovirus Reactivation.Frontiers in cellular and infection microbiology · 2020Review
- Signaling Pathways in Leukemic Stem Cells.Advances in experimental medicine and biology · 2019Review
- Transcription factors FOXO in the regulation of homeostatic hematopoiesis.Current opinion in hematology · 2018Review
- Review
- The impact of Mir-9 regulation in normal and malignant hematopoiesis.Oncology reviews · 2018Article
- Cellular differentiation: Potential insight into butyrate paradox?Molecular & cellular oncology · 2018Article
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5 authors at 1 institution in 1 country.
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Abstract
Transcription factors FOXOs (1, 3, 4) are essential for the maintenance of haematopoietic stem cells. FOXOs are evolutionary conserved substrates of the AKT serine threonine protein kinase that are also phosphorylated by several kinases other than AKT. Specifically, phosphorylation by AKT is known to result in the cytosolic localization of FOXO and subsequent inhibition of FOXO transcriptional activity. In addition to phosphorylation, FOXOs are regulated by a number of other post-translational modifications including acetylation, methylation, redox modulation, and ubiquitination that altogether determine these factors' output. Cumulating evidence raises the possibility that in stem cells, including in haematopoietic stem cells, AKT may not be the dominant regulator of FOXO. To address this question in more detail, we examined gene expression, subcellular localization, and response to AKT inhibition of FOXO1 and FOXO3, the main FOXO expressed in HSPCs (haematopoietic stem and progenitor cells). Here we show that while FOXO1 and FOXO3 transcripts are expressed at similar levels, endogenous FOXO3 protein is mostly nuclear compared to the cytoplasmic localization of FOXO1 in HSPCs. Furthermore, inhibition of AKT does not enhance nuclear localization of FOXO1 nor FOXO3. Nonetheless AKT inhibition in the context of loss of NAD-dependent SIRT1 deacetylase modulates FOXO3 localization in HSPCs. Together, these data suggest that FOXO3 is more active than FOXO1 in primitive haematopoietic stem and multipotent progenitor cells. In addition, they indicate that upstream regulators other than AKT, such as SIRT1, maintain nuclear FOXO localization and activity in HSPCs.
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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.