ArticleProceedings of the National Academy of Sciences of the United States of America2014
Novel antiviral host factor, TNK1, regulates IFN signaling through serine phosphorylation of STAT1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Macrophage-associated kinase signaling in atherosclerosis - a systematic review.Cell communication and signaling : CCS · 2026Pooled it
- Pooled it
- TNK1 is a targetable JAK-independent driver of STAT signaling and inflammation.Genes & development · 2026Article
- IFI35 suppresses the transcription of hepatitis B virus cccDNA minichromosome via promoting HNF4α proteasomal degradation.Journal of biomedical science · 2026Article
- Transcriptomic Analysis of the Antiviral Responses in Ovine Type II Alveolar Epithelial Cells During Early Stage of Bluetongue Virus Infection.Animals : an open access journal from MDPI · 2026Article
- Illuminating the dark kinome: utilizing multiplex peptide activity arrays to functionally annotate understudied kinases.Cell communication and signaling : CCS · 2024Article
- Transcriptional control of interferon-stimulated genes.The Journal of biological chemistry · 2024Review
- Fusion crystallization reveals the behavior of both the 1TEL crystallization chaperone and the TNK1 UBA domain.Structure (London, England : 1993) · 2023Article
- Fusion crystallization reveals the behavior of both the 1TEL crystallization chaperone and the TNK1 UBA domain.bioRxiv : the preprint server for biology · 2023Article
- Persistent hepatic IFN system activation in HBV-HDV infection determines viral replication dynamics and therapeutic response.JCI insight · 2023Article
- Interferon and interferon-stimulated genes in HBV treatment.Frontiers in immunology · 2022Review
- Tyrosine kinase nonreceptor 1 (TNK1) knockdown ameliorates hemorrhage shock-induced kidney injury via inhibiting macrophage M1 polarization.3 Biotech · 2021Article
- TNK1 is a ubiquitin-binding and 14-3-3-regulated kinase that can be targeted to block tumor growth.Nature communications · 2021Article
- Polymorphism rs11867353 of Tyrosine Kinase Non-Receptor 1 (TNK1) Gene Is a Novel Genetic Marker for Alzheimer's Disease.Molecular neurobiology · 2021Article
- A Novel Putative Role of TNK1 in Atherosclerotic Inflammation Implicating the Tyk2/STAT1 Pathway.Mediators of inflammation · 2020Article
- Viperin Differentially Induces Interferon-Stimulated Genes in Distinct Cell Types.Immune network · 2019Article
- Interferon signaling in cancer. Non-canonical pathways and control of intracellular immune checkpoints.Seminars in immunology · 2019Review
- IFN-stimulated P2Y13 protects mice from viral infection by suppressing the cAMP/EPAC1 signaling pathway.Journal of molecular cell biology · 2019Article
- Regulation of Hepatitis C Virus Infection by Cellular Retinoic Acid Binding Proteins through the Modulation of Lipid Droplet Abundance.Journal of virology · 2019Article
- Hepatic IFN-Induced Protein with Tetratricopeptide Repeats Regulation of HCV Infection.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
In response to viral infection, the host induces over 300 IFN-stimulated genes (ISGs), which are the central component of intracellular antiviral innate immunity. Inefficient induction of ISGs contributes to poor control and persistence of hepatitis C virus infection. Therefore, further understanding of the hepatocytic ISG regulation machinery will guide us to an improved management strategy against hepatitis C virus infection. In this study, comprehensive genome-wide, high-throughput cDNA screening for genes regulating ISG expression identified a tyrosine kinase nonreceptor 1 (TNK1) as a unique player in the ISG induction pathway. The immune-modulatory function of TNK1 has never been studied, and this study characterizes its significance in antiviral innate immunity. TNK1 is abundantly expressed in hepatocytes and maintains basal ISG expression. More importantly, TNK1 plays a critical role in type I IFN-mediated ISG induction. We discovered that the activated IFN receptor complex recruits TNK1 from the cytoplasm. TNK1 is then phosphorylated to enhance its kinase activity. The activated TNK1 potentiates JAK-STAT signaling through dual phosphorylation of STAT1 at tyrosine 701 and serine 727 amino acid positions. Our loss-of-function approach demonstrated that TNK1 governs a cluster of ISG expression that defines the TNK1 pathway effector genes. More importantly, TNK1 abundance is inversely correlated to viral replication efficiency and is also a determinant factor for the hepatocytic response to antiviral treatment. Taken together, our studies found a critical but unidentified integrated component of the IFN-JAK-STAT signaling cascade.
Indexed as
Identifiers
What OpenQuestion holds
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.