ArticleThe Journal of biological chemistry2015
Cyclin-dependent kinase-mediated Sox2 phosphorylation enhances the ability of Sox2 to establish the pluripotent state.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- High-throughput Phosphoproteomics Reveals the Role of Phosphorylation in Pluripotency and Phase Separation.Proteomics · 2026Article
- Article
- SOX2 phosphorylation during mitosis limits genomic damage.Genes & development · 2026Article
- AKT1 as a therapeutic target for platinum-resistant SOX2 positive ovarian cancer cells.Scientific reports · 2025Article
- Coupling of stemness maintenance with cell cycle control in stem cells.Frontiers in cell and developmental biology · 2025Review
- CD70 identifies alloreactive T cells and represents a potential target for prevention and treatment of acute GVHD.Blood advances · 2024Article
- Review
- LncRNA NEAT1 controls the lineage fates of BMSCs during skeletal aging by impairing mitochondrial function and pluripotency maintenance.Cell death and differentiation · 2022Article
- G1-phase progression in pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2021Review
- Post-translational modification of SOX family proteins: Key biochemical targets in cancer?Seminars in cancer biology · 2020Review
- Role of cyclins and cyclin-dependent kinases in pluripotent stem cells and their potential as a therapeutic target.Seminars in cell & developmental biology · 2020Review
- Babam2 Regulates Cell Cycle Progression and Pluripotency in Mouse Embryonic Stem Cells as Revealed by Induced DNA Damage.Biomedicines · 2020Article
- Functional characterization of SOX2 as an anticancer target.Signal transduction and targeted therapy · 2020Review
- The recent advances in the mathematical modelling of human pluripotent stem cells.SN applied sciences · 2020Review
- The cell cycle in stem cell proliferation, pluripotency and differentiation.Nature cell biology · 2019Review
- CDK1 Interacts with Sox2 and Promotes Tumor Initiation in Human Melanoma.Cancer research · 2018Article
- Cellular functions of stem cell factors mediated by the ubiquitin-proteasome system.Cellular and molecular life sciences : CMLS · 2018Review
- Regulation of cyclin E1 expression in human pluripotent stem cells and derived neural progeny.Cell cycle (Georgetown, Tex.) · 2018Article
- Cycling to Meet Fate: Connecting Pluripotency to the Cell Cycle.Frontiers in cell and developmental biology · 2018Review
- Cell cycle and pluripotency: Convergence on octamer‑binding transcription factor 4 (Review).Molecular medicine reports · 2017Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sox2 is a key factor in maintaining self-renewal of embryonic stem cells (ESCs) and adult stem cells as well as in reprogramming differentiated cells back into pluripotent or multipotent stem cells. Although previous studies have shown that Sox2 is phosphorylated in human ESCs, the biological significance of Sox2 phosphorylation in ESC maintenance and reprogramming has not been well understood. In this study we have identified new phosphorylation sites on Sox2 and have further demonstrated that Cdk2-mediated Sox2 phosphorylation at Ser-39 and Ser-253 is required for establishing the pluripotent state during reprogramming but is dispensable for ESC maintenance. Mass spectrometry analysis of purified Sox2 protein has identified new phosphorylation sites on two tyrosine and six serine/Threonine residues. Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser-39 and Ser-253 in vitro. Surprisingly, Sox2 phosphorylation at Ser-39 and Ser-253 is dispensable for ESC self-renewal and cell cycle progression. In addition, Sox2 phosphorylation enhances its ability to establish the pluripotent state during reprogramming by working with Oct4 and Klf4. Finally, Cdk2 can also modulate the ability of Oct4, Sox2, and Klf4 in reprogramming fibroblasts back into pluripotent stem cells. Therefore, this study has for the first time demonstrated that Sox2 phosphorylation by Cdk2 promotes the establishment but not the maintenance of the pluripotent state. It might also help explain why the inactivation of CDK inhibitors such as p53, p21, and Arf/Ink4 promotes the induction of pluripotent stem cells.
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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.