ArticlePloS one2015
Dual-Specificity Phosphatase 4 Regulates STAT5 Protein Stability and Helper T Cell Polarization.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- DUSP4 promotes anti-tumor CD8Nature communications · 2026Article
- Splicing-aware scRNA-Seq resolution reveals execution-ready programs in effector Tregs.PLoS computational biology · 2025Article
- Combined Deletion of ZFP36L1 and ZFP36L2 Drives Superior Cytokine Production in T Cells at the Cost of Cell Fitness.European journal of immunology · 2025Article
- Expression profile of mRNAs and miRNAs related to mitogen-activated kinases in HaCaT cell culture treated with lipopolysaccharide a and adalimumab.Cell cycle (Georgetown, Tex.) · 2024Article
- Cytotoxic CD4Med (New York, N.Y.) · 2023Article
- ADSC secretome constrains NK cell activity by attenuating IL-2-mediated JAK-STAT and AKT signaling pathway via upregulation of CIS and DUSP4.Stem cell research & therapy · 2023Article
- An integrative analysis of the single-cell transcriptome identifies DUSP4 as an exhaustion-associated gene in tumor-infiltrating CD8+ T cells.Functional & integrative genomics · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- TIGIT agonism alleviates costimulation blockade-resistant rejection in a regulatory T cell-dependent manner.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Article
- DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases.International journal of molecular sciences · 2021Review
- Aberrant expression of DUSP4 is a specific phenomenon in betel quid-related oral cancer.Medical molecular morphology · 2021Article
- Generation of pralatrexate resistant T-cell lymphoma lines reveals two patterns of acquired drug resistance that is overcome with epigenetic modifiers.Genes, chromosomes & cancer · 2020Article
- Dynamic Roles for IL-2-STAT5 Signaling in Effector and Regulatory CD4Journal of immunology (Baltimore, Md. : 1950) · 2020Review
- DUSP11 Attenuates Lipopolysaccharide-Induced Macrophage Activation by Targeting TAK1.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Assessment of STAT5 as a potential therapy target in enzalutamide-resistant prostate cancer.PloS one · 2020Article
- cAMP Response Element Modulator α Induces Dual Specificity Protein Phosphatase 4 to Promote Effector T Cells in Juvenile-Onset Lupus.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus.Cells · 2019Review
- Genomics of LGL leukemia and select other rare leukemia/lymphomas.Best practice & research. Clinical haematology · 2019Review
- BCL6 corepressor contributes to Th17 cell formation by inhibiting Th17 fate suppressors.The Journal of experimental medicine · 2019Article
- Dual-Specificity Phosphatases in Immunity and Infection: An Update.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune responses are critically regulated by the functions of CD4 helper T cells. Based on their secreted cytokines, helper T cells are further categorized into different subsets like Treg or Th17 cells, which suppress or promote inflammatory responses, respectively. Signals from IL-2 activate the transcription factor STAT5 to promote Treg but suppress Th17 cell differentiation. Our previous results found that the deficiency of a dual-specificity phosphatase, DUSP4, induced STAT5 hyper-activation, enhanced IL-2 signaling, and increased T cell proliferation. In this report, we examined the effects of DUSP4 deficiency on helper T cell differentiation and STAT5 regulation. Our in vivo data showed that DUSP4 mice were more resistant to the induction of autoimmune encephalitis, while in vitro differentiations revealed enhanced iTreg and reduced Th17 polarization in DUSP4-deficient T cells. To study the cause of this altered helper T cell polarization, we performed luciferase reporter assays and confirmed that, as predicted by our previous report, DUSP4 over-expression suppressed the transcription factor activity of STAT5. Surprisingly, we also found that DUSP4-deficient T but not B cells exhibited elevated STAT5 protein levels, and over-expressed DUSP4 destabilized STAT5 in vitro; moreover, this destabilization required the phosphatase activity of DUSP4, and was insensitive to MG132 treatment. Finally, domain-mapping results showed that both the substrate-interacting and the phosphatase domains of DUSP4 were required for its optimal interaction with STAT5, while the coiled-coil domain of STAT5 appeared to hinder this interaction. Our data thus provide the first genetic evidence that DUSP4 is important for helper T cell development. In addition, they also help uncover the novel, DUSP4-mediated regulation of STAT5 protein stability.
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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.