ArticleCellular signalling2016
E3 ubiquitin ligase NKLAM ubiquitinates STAT1 and positively regulates STAT1-mediated transcriptional activity.
Article in Cellular signalling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
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- Parkin Promotes Airway Inflammatory Response to Interferon Gamma.Biomedicines · 2023Article
- An integrated multi-omics analysis of identifies distinct molecular characteristics in pulmonary infections of Pseudomonas aeruginosa.PLoS pathogens · 2023Article
- DIRAS3 enhances RNF19B-mediated RAC1 ubiquitination and degradation in non-small-cell lung cancer cells.iScience · 2023Article
- IRF2 Cooperates with Phosphoprotein of Spring Viremia of Carp Virus to Suppress Antiviral Response in Zebrafish.Journal of virology · 2022Article
- The RING finger protein family in health and disease.Signal transduction and targeted therapy · 2022Review
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- An Overview on Molecular Characterization of Thymic Tumors: Old and New Targets for Clinical Advances.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Stat2 stability regulation: an intersection between immunity and carcinogenesis.Experimental & molecular medicine · 2020Review
- Natural Killer Lytic-Associated Molecule (NKLAM): An E3 Ubiquitin Ligase With an Integral Role in Innate Immunity.Frontiers in physiology · 2020Review
- Mice deficient in NKLAM have attenuated inflammatory cytokine production in a Sendai virus pneumonia model.PloS one · 2019Article
- Reduced inflammation and cytokine production in NKLAM deficient mice during Streptococcus pneumoniae infection.PloS one · 2018Article
- Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA.Nature immunology · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Signal transducer and activator of transcription 1 (STAT1) is critically important for the transcription of a large number of immunologically relevant genes. In macrophages, interferon gamma (IFNγ) signal transduction occurs via the JAK/STAT pathway and ends with the transcription of a number of genes necessary for a successful host immune response. The predominant mechanism of regulation of STAT1 is phosphorylation; however, there is a growing body of evidence that demonstrates STAT1 is also regulated by ubiquitination. In this report we show that JAK1 and STAT1 in macrophages deficient in an E3 ubiquitin ligase termed Natural Killer Lytic-Associated Molecule (NKLAM) are hyperphosphorylated following IFNγ stimulation. We found NKLAM was transiently localized to the IFNγ receptor complex during stimulation with IFNγ, where it bound to and mediated K63-linked ubiquitination of STAT1. In vitro nucleofection studies demonstrated that STAT1-mediated transcription was significantly reduced in NKLAM-KO macrophages. There was no obvious defect in STAT1 nuclear translocation; however, STAT1 from NKLAM-KO macrophages had a reduced ability to bind a functional gamma activation DNA sequence. There was also less mRNA expression of STAT1-mediated genes in NKLAM-KO macrophages treated with IFNγ. Our results demonstrate for the first time that NKLAM is a positive regulator of STAT1-mediated transcriptional activity and is an important component of the innate immune response.
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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.