ArticleThe Journal of biological chemistry2015
Mammalian Sterile 20-like Kinase 1 (Mst1) Enhances the Stability of Forkhead Box P3 (Foxp3) and the Function of Regulatory T Cells by Modulating Foxp3 Acetylation.
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 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Article
- Mammalian Sterile 20-Like Kinase 2 Knockdown Alleviates Neuropathic Pain in Rats by Mitochondrial Protection.Molecular neurobiology · 2025Article
- Article
- 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
- MST1/2 in inflammation and immunity.Cell adhesion & migration · 2023Review
- The role of non-canonical Hippo pathway in regulating immune homeostasis.European journal of medical research · 2023Review
- The hippo kinases MST1/2 in cardiovascular and metabolic diseases: A promising therapeutic target option for pharmacotherapy.Acta pharmaceutica Sinica. B · 2023Review
- Targeting post-translational modifications of Foxp3: a new paradigm for regulatory T cell-specific therapy.Frontiers in immunology · 2023Review
- A Stk4-Foxp3-NF-κB p65 transcriptional complex promotes TScience immunology · 2022Article
- A narrative review for the Hippo-YAP pathway in cancer survival and immunity: the Yin-Yang dynamics.Translational cancer research · 2022Review
- Epigenetic regulation and T-cell responses in endometriosis - something other than autoimmunity.Frontiers in immunology · 2022Review
- Review
- The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease.Cell death & disease · 2021Review
- Interplay Between mTOR and Hippo Signaling in the Ovary: Clinical Choice Guidance Between Different Gonadotropin Preparations for Better IVF.Frontiers in endocrinology · 2021Review
- STK4 Deficiency Impairs Innate Immunity and Interferon Production Through Negative Regulation of TBK1-IRF3 Signaling.Journal of clinical immunology · 2021Article
- Differential transcriptional and functional properties of regulatory T cells in HIV-infected individuals on antiretroviral therapy and long-term non-progressors.Clinical & translational immunology · 2021Article
- Hippo Signal Transduction Mechanisms in T Cell Immunity.Immune network · 2020Review
- Regulatory T Cell Plasticity and Stability and Autoimmune Diseases.Clinical reviews in allergy & immunology · 2020Review
- MST1/2 Balance Immune Activation and Tolerance by Orchestrating Adhesion, Transcription, and Organelle Dynamics in Lymphocytes.Frontiers in immunology · 2020Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulatory T cells (Tregs) play crucial roles in maintaining immune tolerance. The transcription factor Foxp3 is a critical regulator of Treg development and function, and its expression is regulated at both transcriptional and post-translational levels. Acetylation by lysine acetyl transferases/lysine deacetylases is one of the main post-translational modifications of Foxp3, which regulate Foxp3's stability and transcriptional activity. However, the mechanism(s) by which the activities of these lysine acetyl transferases/lysine deacetylases are regulated to preserve proper Foxp3 acetylation during Treg development and maintenance of Treg function remains to be determined. Here we report that Mst1 can enhance Foxp3 stability, its transcriptional activity, and Treg function by modulating the Foxp3 protein at the post-translational level. We discovered that Mst1 could increase the acetylation of Foxp3 by inhibiting Sirt1 activity, which requires the Mst1 kinase activity. We also found that Mst1 could attenuate Sirt1-mediated deacetylation of Foxp3 through directly interacting with Foxp3 to prevent or interfere the interaction between Sirt1 and Foxp3. Therefore, Mst1 can regulate Foxp3 stability in kinase-dependent and kinase-independent manners. Finally, we showed that treatment of Mst1(-/-) Tregs with Ex-527, a Sirt1-specific inhibitor, partially restored the suppressive function of Mst1(-/-) Tregs. Our studies reveal a novel mechanism by which Mst1 enhances Foxp3 expression and Treg function at the post-translational level.
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