ArticleBMC cancer2018
ERK is a negative feedback regulator for IFN-γ/STAT1 signaling by promoting STAT1 ubiquitination.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- Endothelial JAML inhibits inflammation and atherosclerosis through TRIM25-mediated STAT1 ubiquitination.Cellular & molecular biology letters · 2026Article
- IFN-γ2 enhances proliferation and differentiation of muscle cells: a novel target of natural grass feeding mode improving muscle quality in grass carp (Ctenopharyngodon idella).Fish physiology and biochemistry · 2025Article
- SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway.mBio · 2025Article
- Dual regulation of gastrointestinal tumor progression by the IFN-γ/STAT1 pathway and prospects for targeted therapy.Frontiers in oncology · 2025Review
- IL-6/ERK signaling pathway participates in type I IFN-programmed, unconventional M2-like macrophage polarization.Scientific reports · 2023Article
- Dysregulation in IFN-γ signaling and response: the barricade to tumor immunotherapy.Frontiers in immunology · 2023Review
- Article
- SCARF1-Induced Efferocytosis Plays an Immunomodulatory Role in Humans, and Autoantibodies Targeting SCARF1 Are Produced in Patients with Systemic Lupus Erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Identification of Key Signaling Pathways and Genes in Eosinophilic Asthma and Neutrophilic Asthma by Weighted Gene Co-Expression Network Analysis.Frontiers in molecular biosciences · 2022Article
- Review
- Decreased Levels of STAT1 and Interferon-γ-Induced STAT1 Phosphorylation in Rheumatoid Arthritis CD4 and CD8 T Cells.ACR open rheumatology · 2021Article
- Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination.Viruses · 2021Review
- Tyrosine Kinase Inhibitors Stimulate HLA Class I Expression by Augmenting the IFNγ/STAT1 Signaling in Hepatocellular Carcinoma Cells.Frontiers in oncology · 2021Article
- Influence of nNav1.5 on MHC class I expression in breast cancer.Journal of biosciences · 2021Article
- H3K27 acetylation activated-COL6A1 promotes osteosarcoma lung metastasis by repressing STAT1 and activating pulmonary cancer-associated fibroblasts.Theranostics · 2021Article
- NOTCH4 Exhibits Anti-Inflammatory Activity in Activated Macrophages by Interfering With Interferon-γ and TLR4 Signaling.Frontiers in immunology · 2021Article
- Regulation of the MIE Locus During HCMV Latency and Reactivation.Pathogens (Basel, Switzerland) · 2020Review
- Fra-1 Inhibits Cell Growth and the Warburg Effect in Cervical Cancer Cells via STAT1 Regulation of the p53 Signaling Pathway.Frontiers in cell and developmental biology · 2020Article
- ALK and RET Inhibitors Promote HLA Class I Antigen Presentation and Unmask New Antigens within the Tumor Immunopeptidome.Cancer immunology research · 2019Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundWe recently reported that STAT1 plays a tumor suppressor role, and ERK was inversely correlation with STAT1 expression in esophageal squamous cell carcinoma (ESCC). Here, we investigated the mechanism(s) that are responsible for the ERK regulates STAT1 in ESCC.
methodsWe performed the immunoprecipitation (IP) to detect the ubiquitin of STAT1 upon MEK transfection or U0126 treatment and co-IP to confirm the binding of STAT1 and ERK in ESCC cell lines.
resultsWe found evidence that the ubiquitin-proteasome pathway can efficiently degrade STAT1 in ESCC cells, as MG132 treatment rapidly and dramatically increased STAT1 expression in these cells. This process is not dependent on the phosphorylation of the two important STAT1 residues, Y701 and S727, as site-directed mutagenesis of these two sites did not affect STAT1 degradation. We also found that ERK promotes proteasome degradation of STAT1, supported by the observations that pharmacologic inhibition of ERK resulted in a substantial increase of STAT1 whereas expression of constitutively active ERK further reduced the STAT1 protein level. In addition to suppressing STAT1 expression, ERK limited STAT1 signaling by decreasing the production of IFNγ.
conclusionTo conclude, ERK is an effective negative regulator of STAT1 signaling in ESCC, by promoting its proteasome degradation and decreasing IFNγ production. Our data further supports that targeting ERK and/or STAT1 may be useful for treating ESCC.
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