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Updated: Dec 28, 2025
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In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity
Published on: January 29, 2018
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Cross-talk between SUMOylation and ISGylation in response to interferon
Faten El-Asmi1, Francis P McManus2, Carlos Eduardo Brantis-de-Carvalho1
1INSERM UMR-S 1124, Université Paris Descartes, 45 rue des Saints Pères, 75006 Paris, France.
Cytokine
|February 12, 2020
Summary
Interferon (IFN) signaling stabilizes key antiviral proteins, like SAMHD1 and MxB, through SUMOylation. This SUMOylation pathway enhances the host immune response against viral infections, including HIV-1 and HSV-1.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Interferons (IFNs) are crucial for antiviral immunity, inducing IFN-Stimulated Genes (ISGs).
- Cellular SUMOylation and ISGylation are enhanced by IFNs, but their interplay is not fully understood.
Purpose of the Study:
- To investigate the functional relationship between SUMOylation and IFN-induced antiviral responses.
- To identify specific ISG factors regulated by SUMO3 during IFNα stimulation.
Main Methods:
- System-level proteomic analysis of SUMO3-expressing cells stimulated with IFNα.
- Assessing anti-HIV-1 and HSV-1 activities.
- Investigating the role of UBE2L6, TRIM25, and HERC5 in IFNα-induced ISGylation.
- Evaluating the impact of TRIM25 depletion on SUMO3-dependent protein stabilization.
Main Results:
- IFNα stimulation led to the stabilization of multiple ISG factors, including SAMHD1, MxB, GBP1, GBP5, Tetherin/BST2, IFITM, IFIT, and IFI family members.
- SUMO3-dependent stabilization of ISG factors correlated with enhanced anti-HIV-1 and HSV-1 activity.
- IFNα upregulated protein ISGylation by increasing UBE2L6, TRIM25, and HERC5 levels.
- TRIM25 depletion abrogated SUMO3-dependent protein stabilization following IFNα stimulation.
Conclusions:
- SUMO3 plays a novel role in regulating the stability of ISG products.
- The SUMO pathway is critical for controlling the expression and antiviral functions of IFN-induced restriction factors.
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