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Published Online: 12 January 2011

Interferon-Stimulated Gene 15 and the Protein ISGylation System

Publication: Journal of Interferon & Cytokine Research
Volume 31, Issue Number 1

Abstract

Interferon-stimulated gene 15 (ISG15) is one of the most upregulated genes upon Type I interferon treatment or pathogen infection. Its 17 kDa protein product, ISG15, was the first ubiquitin-like modifier identified, and is similar to a ubiquitin linear dimer. As ISG15 modifies proteins in a similar manner to ubiquitylation, protein conjugation by ISG15 is termed ISGylation. Some of the primary enzymes that promote ISGylation are also involved in ubiquitin conjugation. The process to remove ISG15 from its conjugated proteins, termed de-ISGylation, is performed by a cellular ISG15-specific protease, ubiquitin-specific proteases with molecular mass 43 kDa (UBP43)/ubiquitin-specific proteases 18. Relative to ubiquitin, the biological function of ISG15 is still poorly understood, but ISG15 appears to play important roles in various biological and cellular functions. Therefore, there is growing interest in ISG15, as the study of free ISG15 and functional consequences of ISGylation/de-ISGylation may identify useful therapeutic targets. This review highlights recent discoveries and remaining questions important to understanding the biological functions of ISG15.

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cover image Journal of Interferon & Cytokine Research
Journal of Interferon & Cytokine Research
Volume 31Issue Number 1January 2011
Pages: 119 - 130
PubMed: 21190487

History

Published online: 12 January 2011
Published in print: January 2011
Published ahead of print: 29 December 2010
Accepted: 11 August 2010
Received: 11 August 2010

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Dongxian Zhang
Sanford-Burnham Medical Research Institute, La Jolla, California.
Dong-Er Zhang
Division of Biological Sciences, Department of Pathology, Moores UCSD Cancer Center, University of California San Diego, La Jolla, California.

Notes

Address correspondence to:Dr. Dong-Er ZhangDivision of Biological SciencesDepartment of PathologyMoores UCSD Cancer CenterUniversity of California San DiegoMail Drop 0815, Room 53283855 Health Sciences DriveLa Jolla, CA 92093E-mail: [email protected]

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No competing financial interests exist.

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