Document Detail


ISG15 and immune diseases.
MedLine Citation:
PMID:  20153823     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
ISG15, the product of interferon (IFN)-stimulated gene 15, is the first identified ubiquitin-like protein, consisting of two ubiquitin-like domains. ISG15 is synthesized as a precursor in certain mammals and, therefore, needs to be processed to expose the C-terminal glycine residue before conjugation to target proteins. A set of three-step cascade enzymes, an E1 enzyme (UBE1L), an E2 enzyme (UbcH8), and one of several E3 ligases (e.g., EFP and HERC5), catalyzes ISG15 conjugation (ISGylation) of a specific protein. These enzymes are unique among the cascade enzymes for ubiquitin and other ubiquitin-like proteins in that all of them are induced by type I IFNs or other stimuli, such as exposure to viruses and lipopolysaccharide. Mass spectrometric analysis has led to the identification of several hundreds of candidate proteins that can be conjugated by ISG15. Some of them are type I IFN-induced proteins, such as PKR and RIG-I, and some are the key regulators that are involved in IFN signaling, such as JAK1 and STAT1, implicating the role of ISG15 and its conjugates in type I IFN-mediated innate immune responses. However, relatively little is known about the functional significance of ISG15 induction due to the lack of information on the consequences of its conjugation to target proteins. Here, we describe the recent progress made in exploring the biological function of ISG15 and its reversible modification of target proteins and thus in their implication in immune diseases.
Authors:
Young Joo Jeon; Hee Min Yoo; Chin Ha Chung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2010-02-12
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1802     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-03-15     Completed Date:  2010-05-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  485-96     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Affiliation:
School of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Cytokines / physiology*
Humans
Immune System Diseases / immunology*
Ubiquitins / physiology*
Chemical
Reg. No./Substance:
0/Cytokines; 0/Ubiquitins; 60267-61-0/ISG15 protein, human

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