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ISG15: a ubiquitin-like enigma
1Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Frontiers in Bioscience : a Journal and Virtual Library
|June 23, 2005
Summary
Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like modifier with largely unknown functions. Recent discoveries of ISG15-modifying enzymes and their roles in immunity and disease highlight its therapeutic potential.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- ISG15, a ubiquitin-like modifier, was discovered in 1979 but its functions remain largely unknown.
- ISG15 conjugation is implicated in innate immunity, interferon signaling, pregnancy, and cancer.
- The enzymes responsible for ISG15 activation and conjugation have recently been identified.
Purpose of the Study:
- To review the discovery and known functions of ISG15.
- To highlight recent findings on ISG15-modifying enzymes and their implications.
- To identify knowledge gaps and challenges in understanding ISG15's biologic roles.
Main Methods:
- Literature review of ISG15 research.
- Analysis of recent studies on ISG15 conjugation and deconjugation enzymes.
- Summary of findings from knockout mouse models.
Main Results:
- ISG15 conjugation enzymes are shared with the ubiquitin system.
- A specific ISG15 protease knockout in mice reduces lifespan and increases sensitivity to interferon and LPS.
- ISG15 modification impacts signal transduction and innate immunity.
Conclusions:
- The ISG15 modification system plays crucial roles in the immune response.
- Understanding ISG15 pathways may reveal novel therapeutic targets for immune-related diseases and cancer.
- Further research is needed to elucidate ISG15's complete biologic functions.