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.
journal_name
Cytokinejournal_title
Cytokineauthors
El-Asmi F,McManus FP,Brantis-de-Carvalho CE,Valle-Casuso JC,Thibault P,Chelbi-Alix MKdoi
10.1016/j.cyto.2020.155025subject
Has Abstractpub_date
2020-05-01 00:00:00pages
155025eissn
1043-4666issn
1096-0023pii
S1043-4666(20)30041-7journal_volume
129pub_type
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