ArticleThe Journal of biological chemistry2012
STAT3 protein interacts with Class O Forkhead transcription factors in the cytoplasm and regulates nuclear/cytoplasmic localization of FoxO1 and FoxO3a proteins in CD4(+) T cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 118 citations in OpenAlex.
- Polydatin mitigates cigarette smoke-induced pulmonary apoptosis by regulating Bim via FoxO3 post-translational modifications and modulating the gut microenvironment.Biology direct · 2026Article
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Mitigating psychological stress-induced cardiac injury: The impact of CB2R agonists on endoplasmic reticulum stress and mitophagy.Biochemistry and biophysics reports · 2026Article
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Loss of miR-424 and miR-503 promotes decidualization of human endometrial stromal cells by increasing SCARA5 expression.Medical molecular morphology · 2025Article
- Nck1 regulates the in vitro development of human regulatory T cells through AKT pathway.Clinical and experimental immunology · 2025Article
- Integrative modeling of FOXO-mediated autophagy in NSCLC: linking cGAS-STING signaling to IL-6 dynamics.Frontiers in oncology · 2025Article
- STAT3 inhibition recovers regeneration of aged muscles by restoring autophagy in muscle stem cells.Life science alliance · 2024Article
- Article
- Transplantation of the LRP1Stem cell research & therapy · 2024Article
- The role of Foxo3a in neuron-mediated cognitive impairment.Frontiers in molecular neuroscience · 2024Review
- FOXO1-mediated nuclear sequestration of STAT3 and AKT1 triggers FOXO3-dependent autophagic death in hypoxic granulosa cells.International journal of biological sciences · 2024Article
- Menstrual blood-derived endometrial stem cell, a unique and promising alternative in the stem cell-based therapy for chemotherapy-induced premature ovarian insufficiency.Stem cell research & therapy · 2023Review
- FOXO1 is a master regulator of CAR T memory programming.Research square · 2023Article
- IL-21 shapes germinal center polarization via light zone B cell selection and cyclin D3 upregulation.The Journal of experimental medicine · 2023Article
- [8] and [10]-Gingerol reduces urothelial damage in ifosfamide-induced hemorrhagic cystitis via JAK/STAT/FOXO signaling pathway via IL-10.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Transcriptional regulation of autophagy and its implications in human disease.Cell death and differentiation · 2023Review
- Phosphorylation of STAT3 at Tyr705 contributes to TFEB-mediated autophagy-lysosomal pathway dysfunction and leads to ischemic injury in rats.Cellular and molecular life sciences : CMLS · 2023Article
- Apoptotic vesicles resist oxidative damage in noise-induced hearing loss through activation of FOXO3a-SOD2 pathway.Stem cell research & therapy · 2023Article
- LncRNA DANCR restrained the survival ofFrontiers in microbiology · 2023Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
An important feature of the adaptive immune response is its remarkable capacity to regulate the duration of inflammatory responses, and effector T cells have been shown to limit excessive immune responses by producing anti-inflammatory cytokines such as IL-10 and IL-27. However, how anti-inflammatory cytokines mediate their suppressive activities is not well understood. In this study, we show that STAT3 contributes to mechanisms that control the duration of T cell proliferation by regulating the subcellular location of FoxO1 and FoxO3a, two Class O Forkhead transcription factors that mediate lymphocyte quiescence and inhibit T cell activation. We show that active FoxO1 and FoxO3a reside exclusively in the nucleus of naïve T cells whereas inactive pFoxO1 and pFoxO3a were most abundant in activated T cells and sequestered in their cytoplasm in association with unphosphorylated STAT3 (U-STAT3) and 14-3-3. We further show that FoxO1/FoxO3a rapidly relocalized into the nucleus in response to pSTAT3 activation by IL-6 or IL-10, and the accumulation of FoxO1/FoxO3a in their nuclei coincided with increased expression of p27(Kip1) and p21(WAF1). STAT3 inhibitors completely abrogated cytokine-induced translocation of FoxO1/FoxO3a into the nucleus. In naïve or resting STAT3-deficient T cells, expression of pFoxO1/pFoxO3a was predominantly in the cytoplasm and correlated with defects in p27(Kip1) and p21(WAF1) expression, suggesting requirement of STAT3 for importation or retention of FoxO in the nucleus and attenuation of lymphocyte proliferation. Taken together, these results suggest that U-STAT3 collaborates with 14-3-3 to sequester pFoxO1/pFoxO3a in cytoplasm and thus prolong T cell activation, whereas pSTAT3 activation by anti-inflammatory cytokines would curtail the duration of TCR activation and re-establish lymphocyte quiescence by inducing nuclear localization of FoxO1/FoxO3a and FoxO-mediated expression of growth-inhibitory proteins.
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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.