ArticleThe Journal of biological chemistry2019
Sirtuin 2-mediated deacetylation of cyclin-dependent kinase 9 promotes STAT1 signaling in type I interferon responses.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages.Immunity · 2026Article
- The function and mechanism of protein acylation in the regulation of viral infection.Virulence · 2025Review
- Interferon-driven Metabolic Reprogramming and Tumor Microenvironment Remodeling.Immune network · 2025Review
- Unraveled role of TLR7-mediated interferon signaling activation in COVID-19.Frontiers in cellular and infection microbiology · 2025Review
- Increased expression of cathepsin C in airway epithelia exacerbates airway remodeling in asthma.JCI insight · 2024Article
- Targeting CHAF1B Enhances IFN Activity against Myeloproliferative Neoplasm Cells.Cancer research communications · 2023Article
- Targeting cyclin-dependent kinase 9 in cancer therapy.Acta pharmacologica Sinica · 2022Review
- Discovery of a signaling feedback circuit that defines interferon responses in myeloproliferative neoplasms.Nature communications · 2022Article
- Review
- Review
- Acetyl-bufalin shows potent efficacy against non-small-cell lung cancer by targeting the CDK9/STAT3 signalling pathway.British journal of cancer · 2021Article
- Article
- Acetylation in Tumor Immune Evasion Regulation.Frontiers in pharmacology · 2021Review
- CDK8 Fine-Tunes IL-6 Transcriptional Activities by Limiting STAT3 Resident Time at the Gene Loci.Cell reports · 2020Article
- Article
- Gestation and breastfeeding in schistosomotic mice differentially alters the expression of histone deacetylases (HDACs) in adult offspring.Memorias do Instituto Oswaldo Cruz · 2020Article
- Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways.Frontiers in immunology · 2020Review
- The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy.Frontiers in cell and developmental biology · 2020Review
- AFF1 acetylation by p300 temporally inhibits transcription during genotoxic stress response.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Interferon signaling in cancer. Non-canonical pathways and control of intracellular immune checkpoints.Seminars in immunology · 2019Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
Abstract
Type I interferons (IFNs) induce expression of multiple genes that control innate immune responses to invoke both antiviral and antineoplastic activities. Transcription of these interferon-stimulated genes (ISGs) occurs upon activation of the canonical Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathways. Phosphorylation and acetylation are both events crucial to tightly regulate expression of ISGs. Here, using mouse embryonic fibroblasts and an array of biochemical methods including immunoblotting and kinase assays, we show that sirtuin 2 (SIRT2), a member of the NAD-dependent protein deacetylase family, is involved in type I IFN signaling. We found that SIRT2 deacetylates cyclin-dependent kinase 9 (CDK9) in a type I IFN-dependent manner and that the CDK9 deacetylation is essential for STAT1 phosphorylation at Ser-727. We also found that SIRT2 is subsequently required for the transcription of ISGs and for IFN-driven antiproliferative responses in both normal and malignant cells. These findings establish the existence of a previously unreported signaling pathway whose function is essential for the control of JAK-STAT signaling and the regulation of IFN responses. Our findings suggest that targeting sirtuin activities may offer an avenue in the development of therapies for managing immune-related diseases and cancer.
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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.