ArticleProceedings of the National Academy of Sciences of the United States of America2012
The protein kinase Akt1 regulates the interferon response through phosphorylation of the transcriptional repressor EMSY.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 81 citations in OpenAlex.
- Akt Signaling Pathway Is Activated in the Minor Salivary Glands of Patients with Primary Sjögren's Syndrome.International journal of molecular sciences · 2021Trial
- Poxvirus infection triggers remodeling of host m⁶A epitranscriptome and benefits from the m⁶A regulatory responses.Virology journal · 2026Article
- miR-451-targeted PSMB8 promotes PRRSV infection by degrading IRF3.Journal of virology · 2024Article
- Targeting EMSY-mediated methionine metabolism is a potential therapeutic strategy for triple-negative breast cancer.Cell reports. Medicine · 2024Article
- EMSY stabilization in KEAP1-mutant lung cancer disrupts genome stability and type I interferon signaling.Cell death and differentiation · 2023Article
- AKT inhibition in the central nervous system induces signaling defects resulting in psychiatric symptomatology.Cell & bioscience · 2022Article
- Article
- Akt isoforms in the immune system.Frontiers in immunology · 2022Review
- Genetics and Epigenetics in Allergic Rhinitis.Genes · 2021Review
- Phosphor-IWS1-dependent U2AF2 splicing regulates trafficking of CAR-E-positive intronless gene mRNAs and sensitivity to viral infection.Communications biology · 2021Article
- Identification of poly(ADP-ribose) polymerase 9 (PARP9) as a noncanonical sensor for RNA virus in dendritic cells.Nature communications · 2021Article
- Conserved IFN Signature between Adult and Pediatric Eosinophilic Esophagitis.Journal of immunology (Baltimore, Md. : 1950) · 2021Observational
- Integrating Proteomes for Lung Tissues and Lavage Reveals Pathways That Link Responses in Allergen-Challenged Mice.ACS omega · 2021Article
- Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets.Frontiers in physiology · 2021Review
- Host transcriptomic profiling of COVID-19 patients with mild, moderate, and severe clinical outcomes.Computational and structural biotechnology journal · 2021Article
- Akt3 induces oxidative stress and DNA damage by activating the NADPH oxidase via phosphorylation of p47Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Targeting the PI3K pathway and DNA damage response as a therapeutic strategy in ovarian cancer.Cancer treatment reviews · 2020Review
- EMSY expression affects multiple components of the skin barrier with relevance to atopic dermatitis.The Journal of allergy and clinical immunology · 2019Article
- BRCA2 abrogation triggers innate immune responses potentiated by treatment with PARP inhibitors.Nature communications · 2019Article
- Assessing the Risk Factors for Refractory Eosinophilic Esophagitis in Children and Adults.Gastroenterology research and practice · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The protein kinases Akt1, Akt2, and Akt3 possess nonredundant signaling properties, few of which have been investigated. Here, we present evidence for an Akt1-dependent pathway that controls interferon (IFN)-regulated gene expression and antiviral immunity. The target of this pathway is EMSY, an oncogenic interacting partner of BRCA2 that functions as a transcriptional repressor. Overexpression of EMSY in hTERT-immortalized mammary epithelial cells, and in breast and ovarian carcinoma cell lines, represses IFN-stimulated genes (ISGs) in a BRCA2-dependent manner, whereas its knockdown has the opposite effect. EMSY binds to the promoters of ISGs, suggesting that EMSY functions as a direct transcriptional repressor. Akt1, but not Akt2, phosphorylates EMSY at Ser209, relieving EMSY-mediated ISG repression. The Akt1/EMSY/ISG pathway is activated by both viral infection and IFN, and it inhibits the replication of HSV-1 and vesicular stomatitis virus (VSV). Collectively, these data define an Akt1-dependent pathway that contributes to the full activation of ISGs by relieving their repression by EMSY and BRCA2.
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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.