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Updated: Jul 15, 2026
09:29
Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications
Published on: May 18, 2017
Understanding protein ISGylation, a multifaceted posttranslational modification.
David Joseph Shirley1, Euna Yoo1
1Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Cell Chemical Biology
|July 13, 2026
Summary
Interferon-induced protein ISG15 (Interferon-Stimulated Gene 15) is a ubiquitin-like modifier crucial for innate immunity. Its conjugation (ISGylation) and removal (deISGylation) impact various cellular processes and are implicated in diseases.
Area of Science:
- Molecular Biology
- Immunology
- Biochemistry
Background:
- Interferon signaling induces ISG15 (Interferon-Stimulated Gene 15), a ubiquitin-like modifier.
- ISG15 conjugation (ISGylation) involves a specific enzymatic cascade (UBE1L, UBE2L6, E3 ligases) and is reversed by deISGylases like USP18.
- ISGylation regulates protein stability, interactions, autophagy, transcription, DNA damage response, and innate immunity.
Purpose of the Study:
- To elucidate the molecular mechanisms and biological significance of ISG15 modification.
- To identify key enzymes and substrates involved in ISGylation and deISGylation.
- To explore the pathophysiological relevance of dysregulated ISGylation in various diseases.
Main Methods:
- Chemical biology approaches.
- Mass spectrometry-based proteomics.
- Enzyme characterization and substrate mapping.
Main Results:
- Characterization of enzymes mediating ISGylation and deISGylation.
- Identification and mapping of ISGylated proteins and conjugation sites.
- Demonstration of ISGylation's broad impact on cellular functions.
Conclusions:
- ISGylation is a critical post-translational modification with wide-ranging cellular and molecular consequences.
- Dysregulation of ISGylation pathways is linked to cancer, infections, neurodegeneration, and inflammatory diseases.
- Understanding ISGylation is vital for developing therapeutic strategies for associated pathologies.
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