ArticleThe Journal of biological chemistry2013
Foxp3 protein stability is regulated by cyclin-dependent kinase 2.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
69 citing papers in PubMed, 110 citations in OpenAlex.
- Article
- Review
- Review
- Kinase signaling in the control of regulatory T cell function: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Identification and validation of diagnostic genesFrontiers in immunology · 2025Article
- Article
- Phenotypic divergence between broiler and layer chicken lines is regulated at the molecular level during development.BMC genomics · 2024Article
- Synthesis, docking, MD simulation, ADMET, drug likeness, and DFT studies of novel furo[2,3-b]indol-3a-ol as promising Cyclin-dependent kinase 2 inhibitors.Scientific reports · 2024Article
- Epigenetic regulation of human FOXP3+ Tregs: from homeostasis maintenance to pathogen defense.Frontiers in immunology · 2024Review
- Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point?Frontiers in immunology · 2024Review
- Treg plasticity and human diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Myeloid-intrinsic cell cycle-related kinase drives immunosuppression to promote tumorigenesis.iScience · 2023Article
- Development and function of FOXP3+ regulators of immune responses.Clinical and experimental immunology · 2023Article
- T cells in health and disease.Signal transduction and targeted therapy · 2023Review
- Targeting post-translational modifications of Foxp3: a new paradigm for regulatory T cell-specific therapy.Frontiers in immunology · 2023Review
- Regulatory T Cells in Autoimmune Vasculitis.Frontiers in immunology · 2022Review
- CD98-induced CD147 signaling stabilizes the Foxp3 protein to maintain tissue homeostasis.Cellular & molecular immunology · 2021Article
- Activation of AMPKα1 is essential for regulatory T cell function and autoimmune liver disease prevention.Cellular & molecular immunology · 2021Article
- Cyclin E in normal physiology and disease states.Trends in cell biology · 2021Review
- Targeting cell-cycle machinery in cancer.Cancer cell · 2021Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Foxp3 is a transcription factor required for the development of regulatory T cells (Treg). Mice and humans with a loss of Foxp3 function suffer from uncontrolled autoimmunity and inflammatory disease. Expression of Foxp3 is necessary for the anti-inflammatory capacity of Treg, but whether Foxp3 activity is further subject to regulation by extracellular signals is unclear. The primary structure of Foxp3 contains four cyclin-dependent kinase (CDK) motifs (Ser/Thr-Pro) within the N-terminal repressor domain, and we show that CDK2 can partner with cyclin E to phosphorylate Foxp3 at these sites. Consistent with our previous demonstration that CDK2 negatively regulates Treg function, we find that mutation of the serine or threonine at each CDK motif to alanine (S/T→A) results in enhanced Foxp3 protein stability in CD4(+) T cells. T cells expressing the S/T→A mutant of Foxp3 showed enhanced induction (e.g. CD25) and repression (e.g. IL2) of canonical Foxp3-responsive genes, exhibited an increased capacity to suppress conventional T cell proliferation in vitro, and were highly effective at ameliorating colitis in an in vivo model of inflammatory bowel disease. These results indicate that CDK2 negatively regulates the stability and activity of Foxp3 and implicate CDK-coupled receptor signal transduction in the control of regulatory T cell function and stability.
Indexed as
Identifiers
What OpenQuestion holds
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.