Document Detail


Protein ISGylation modulates the JAK-STAT signaling pathway.
MedLine Citation:
PMID:  12600939     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Genes & development     Volume:  17     ISSN:  0890-9369     ISO Abbreviation:  Genes Dev.     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-02-25     Completed Date:  2003-03-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  455-60     Citation Subset:  IM    
Affiliation:
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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
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