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Cytokine. 2020 Feb 7;129:155025. doi: 10.1016/j.cyto.2020.155025. [Epub ahead of print]

Cross-talk between SUMOylation and ISGylation in response to interferon.

Author information

1
INSERM UMR-S 1124, Université Paris Descartes, 45 rue des Saints Pères, 75006 Paris, France.
2
Institute for Research in Immunology and Cancer, Québec, Canada.
3
Institut Pasteur, Unité HIV Inflammation et Persistance, Paris, France.
4
Institute for Research in Immunology and Cancer, Québec, Canada; University of Montréal, Department of Chemistry, Québec, Canada. Electronic address: pierre.thibault@umontreal.ca.
5
INSERM UMR-S 1124, Université Paris Descartes, 45 rue des Saints Pères, 75006 Paris, France. Electronic address: mounira.chelbi-alix@parisdescartes.fr.

Abstract

Interferon (IFN) plays a central role in regulating host immune response to viral pathogens through the induction of IFN-Stimulated Genes (ISGs). IFN also enhances cellular SUMOylation and ISGylation, though the functional interplay between these modifications remains unclear. Here, we used a system-level approach to profile global changes in protein abundance in SUMO3-expressing cells stimulated by IFNα. These analyses revealed the stabilization of several ISG factors including SAMHD1, MxB, GBP1, GBP5, Tetherin/BST2 and members of IFITM, IFIT and IFI families. This process was correlated with enhanced IFNα-induced anti-HIV-1 and HSV-1 activities. Also IFNα upregulated protein ISGylation through increased abundance of E2 conjugating enzyme UBE2L6, and E3 ISG15 ligases TRIM25 and HERC5. Remarkably, TRIM25 depletion blocked SUMO3-dependent protein stabilization in response to IFNα. Our data identify a new mechanism by which SUMO3 regulates ISG product stability and reinforces the relevance of the SUMO pathway in controlling both the expression and functions of the restriction factors and IFN antiviral response.

KEYWORDS:

HIV-1; HSV-1; IFN; ISG15; Restriction factors; SUMO; Ubiquitin

PMID:
32044670
DOI:
10.1016/j.cyto.2020.155025

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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