ArticleProceedings of the National Academy of Sciences of the United States of America2005
Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 249 papers.
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Who cites it
249 citing papers in PubMed, 462 citations in OpenAlex.
- Understanding protein ISGylation, a multifaceted posttranslational modification.Cell chemical biology · 2026Review
- Herpesviruses hijack ISGylation to promote viral capsid assembly.Science advances · 2026Article
- Article
- BTV Remodels the oISG15-Association Proteome.Microorganisms · 2026Article
- Identification of ovine proteins targeted by pregnancy-induced ISGylation and inference on function I: endometrium†.Biology of reproduction · 2026Article
- The capping arms race: evolutionary interplay between IFIT proteins and viral molecular mimicry.Molecular biology reports · 2026Review
- A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages.Immunity · 2026Article
- Analyzing the Molecular Signature Genes and Pathways of Dengue Fever, Dengue Hemorrhagic Fever and Dengue Shock Syndrome Caused by Dengue Virus in India.Molecular biotechnology · 2026Article
- Beyond Viral Restriction: The Metabolic Dimensions of Interferon-Stimulated Genes in Antiviral Immunity.Viruses · 2026Review
- METTL3 abrogation promotes glioma progression through regulating the ISG15-FASN axis-mediated lipid metabolism in macrophages.Nature communications · 2026Article
- Interferon-induced protein ISG15 in the central nervous system, quo vadis?FEBS letters · 2025Review
- Osteopontin derived from hypoxia-induced M2 macrophages promotes osteosarcoma progression through modulation of EGR3/ISG15 signaling and RIG-I expression.Journal of translational medicine · 2025Article
- Human protein interaction networks of ancestral and variant SARS-CoV-2 in organ-specific cells and bodily fluids.Nature communications · 2025Article
- Unveiling the crossroads of STING signaling pathway and metabolic reprogramming: the multifaceted role of the STING in the TME and new prospects in cancer therapies.Cell communication and signaling : CCS · 2025Review
- Beclin 1 prevents ISG15-mediated cytokine storms to secure fetal hematopoiesis and survival.The Journal of clinical investigation · 2025Article
- Chemical tools to define and manipulate interferon-inducible Ubl protease USP18.Nature communications · 2025Article
- The enhancer RNA, AANCR, regulates APOE expression in astrocytes and microglia.Nucleic acids research · 2024Article
- Interferon-tau infusion into the ovine corpus luteum delays luteolysis†.Biology of reproduction · 2024Article
- Expression of MxA in esophageal cancer cell lines can influence sensitivity to chemotherapeutic agents but this does not require apoptosis.Cancer medicine · 2024Article
- ISG15 blocks cardiac glycolysis and ensures sufficient mitochondrial energy production during Coxsackievirus B3 infection.Cardiovascular research · 2024Article
189 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
IFN-alpha/beta plays an essential role in innate immunity against viral and bacterial infection. Among the proteins induced by IFN-alpha/beta are the ubiquitin-like ISG15 protein and its E1- (Ube1L) and E2- (UbcH8) conjugating enzymes, leading to the conjugation of ISG15 to cellular proteins. It is likely that ISG15 conjugation plays an important role in antiviral response because a human virus, influenza B virus, inhibits ISG15 conjugation. However, the biological function of ISG15 modification remains unknown, largely because only a few human ISG15 target proteins have been identified. Here we purify ISG15-modified proteins from IFN-beta-treated human (HeLa) cells by using double-affinity selection and use mass spectroscopy to identify a large number (158) of ISG15 target proteins. Eight of these proteins were subjected to further analysis and verified to be ISG15 modified in IFN-beta-treated cells, increasing the likelihood that most, if not all, targets identified by mass spectroscopy are bona fide ISG15 targets. Several of the targets are IFN-alpha/beta-induced antiviral proteins, including PKR, MxA, HuP56, and RIG-I, providing a rationale for the inhibition of ISG15 conjugation by influenza B virus. Most targets are constitutively expressed proteins that function in diverse cellular pathways, including RNA splicing, chromatin remodeling/polymerase II transcription, cytoskeleton organization and regulation, stress responses, and translation. These results indicate that ISG15 conjugation impacts nuclear as well as cytoplasmic functions. By targeting a wide array of constitutively expressed proteins, ISG15 conjugation greatly extends the repertoire of cellular functions that are affected by IFN-alpha/beta.
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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.