| Protein ISGylation modulates the JAK-STAT signaling pathway. | |
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MedLine Citation:
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PMID: 12600939 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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ISG15 is one of the most strongly induced genes upon viral infection, type I interferon (IFN) stimulation, and lipopolysaccharide (LPS) stimulation. Here we report that mice lacking UBP43, a protease that removes ISG15 from ISGylated proteins, are hypersensitive to type I IFN. Most importantly, in UBP43-deficient cells, IFN-beta induces a prolonged Stat1 tyrosine phosphorylation, DNA binding, and IFN-mediated gene activation. Furthermore, restoration of ISG15 conjugation in protein ISGylation-defective K562 cells increases IFN-stimulated promoter activity. These findings identify UBP43 as a novel negative regulator of IFN signaling and suggest the involvement of protein ISGylation in the regulation of the JAK-STAT pathway. |
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Authors:
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Oxana A Malakhova; Ming Yan; Michael P Malakhov; Youzhong Yuan; Kenneth J Ritchie; Keun Il Kim; Luke F Peterson; Ke Shuai; Dong-Er Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Genes & development Volume: 17 ISSN: 0890-9369 ISO Abbreviation: Genes Dev. Publication Date: 2003 Feb |
Date Detail:
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Created Date: 2003-02-25 Completed Date: 2003-03-27 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8711660 Medline TA: Genes Dev Country: United States |
Other Details:
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Languages: eng Pagination: 455-60 Citation Subset: IM |
Affiliation:
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Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects Bone Marrow Transplantation Cytokines / drug effects, metabolism* DNA-Binding Proteins / metabolism* Endopeptidases / genetics*, metabolism Hematopoietic Stem Cells / drug effects Humans Interferon Inducers / pharmacology Interferon-beta / metabolism, pharmacology Janus Kinase 1 K562 Cells / drug effects Ligases / genetics, metabolism Mice Mice, Inbred C57BL Mice, Mutant Strains Phosphorylation Poly I-C / pharmacology Promoter Regions, Genetic Protein-Tyrosine Kinases / drug effects, metabolism* STAT1 Transcription Factor Signal Transduction Trans-Activators / metabolism* Tyrosine Ubiquitin-Protein Ligases Ubiquitins* / analogs & derivatives* |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/DNA-Binding Proteins; 0/G1p2 protein, mouse; 0/Interferon Inducers; 0/Jak1 protein, mouse; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/Stat1 protein, mouse; 0/Trans-Activators; 0/Ubiquitins; 24939-03-5/Poly I-C; 55520-40-6/Tyrosine; 60267-61-0/ISG15 protein, human; 77238-31-4/Interferon-beta; EC 2.7.1.112/JAK1 protein, human; EC 2.7.10.1/Janus Kinase 1; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 3.4.-/Endopeptidases; EC 3.4.99.-/USP18 protein, human; EC 3.4.99.-/Usp18 protein, mouse; EC 6.-/Ligases; EC 6.3.2.19/Ubiquitin-Protein Ligases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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