ISGylation: is our genome yearning for such a modification?
Chen Z. Li Z. Wang Y. Dushimova Z. Gulnara K. Takeda S. Zhou Z. Xu X.
1 November 2025Science Press
Acta Biochimica et Biophysica Sinica
2025#57Issue 111743 - 1757 pp.
ISGylation is the post-translational modification of protein substrates covalently conjugated with the ubiquitin-like protein, interferon-stimulated gene 15 (ISG15). Although initially linked to antiviral immunity, recent evidence highlights important roles for ISGylation in various biological processes, such as maintaining genomic stability, promoting tumourigenesis, and being involved in other pathological conditions. In this review, we examine the molecular mechanisms underlying ISGylation, its interplay with other post-translational modifications, and its involvement in diverse biological and pathological processes. We propose future research directions to advance the field and discuss how ISGylation might be harnessed to ensure human health, particularly genome instability-associated diseases.
antibacterial immunity , antiviral immunity , genomic stability , ISG15 , ISGylation
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Shenzhen University General Hospital-Dehua Hospital Joint Research Center on Precision Medicine (sgh-dhhCPM), Dehua Hospital, Dehua, 362500, China
State Key Laboratory of Agrobiotechnology and MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China
Guangdong Key Laboratory for Genome Stability & Disease Prevention and Carson International Cancer Center, Marshall Laboratory of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, China
Al-Farabi Kazakh National University, 71 Al-Farabi Avenue, Almaty, 050040, Kazakhstan
School of Biomedical Sciences, University of Hong Kong, 999077, Hong Kong
Shenzhen University General Hospital-Dehua Hospital Joint Research Center on Precision Medicine (sgh-dhhCPM)
State Key Laboratory of Agrobiotechnology and MOA Key Laboratory of Soil Microbiology
Guangdong Key Laboratory for Genome Stability & Disease Prevention and Carson International Cancer Center
Al-Farabi Kazakh National University
School of Biomedical Sciences
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