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Published on: July 5, 2021
ISG15 and ISGylation in Human Diseases
Oygul Mirzalieva1, Meredith Juncker1, Joshua Schwartzenburg1
1Department of Biochemistry and Molecular Biology, LSUHSC-School of Medicine, 1901 Perdido Street, New Orleans, LA 70112, USA.
Interferon-Stimulated Gene 15 (ISG15) is a crucial protein involved in immune responses and human diseases. Its dual role as a biomarker and therapeutic target highlights its significance in cancer and neurodegenerative disorders.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Type I Interferons (IFNs) induce over 500 IFN-stimulated genes (ISGs).
- ISG15 is an early ISG, functioning as a free protein or conjugated via ISGylation.
- ISG15 shares structural and functional similarities with ubiquitin.
Purpose of the Study:
- To review the multifaceted roles of ISG15 and ISGylation in human diseases.
- To highlight ISG15's potential as a diagnostic/prognostic biomarker and therapeutic target.
- To trace the scientific journey of ISG15 from basic research to clinical applications.
Main Methods:
- Literature review of ISG15 research over three decades.
- Analysis of ISG15's structure, function, and conjugation (ISGylation).
- Examination of ISG15's involvement in various human pathologies.
Main Results:
- ISG15 expression is dysregulated in cancers, neurodegenerative diseases, and inflammatory conditions.
- ISG15 and ISGylation exhibit dual roles (inhibitory/stimulatory) in disease pathogenesis.
- ISG15 influences cancer cell proliferation, migration, metastasis, and drug sensitivity.
Conclusions:
- ISG15 is a "double-edged sword" with complex roles in disease.
- Elevated ISG15 levels in specific conditions suggest its utility as a biomarker.
- ISG15 and ISGylation represent promising therapeutic targets for various ailments.
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