Cross-talk between SUMOylation and ISGylation in response to interferon

El-Asmi, Faten; McManus, Francis P.; Brantis-de-Carvalho, Carlos Eduardo; Valle-Casuso, José Carlos; Thibault, Pierre; Chelbi-Alix, Mounira K.

doi:10.1016/j.cyto.2020.155025

Cited by 20 publications

(14 citation statements)

References 59 publications

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“…TRIM19/PML mediates global sumoylation [92], and TRIM25 functions as an ISG15 E3 ligase that mediates ISGylation [124]. Further, TRIM25 has been recently reported to be required for the stability of several ISG products [186]. The zinc-finger antiviral protein ZAP, as an ISG, is activated by TRIM25-mediated ubiquitination to inhibit viral genome translation [125].…”

Section: Trims In Regulating the Jak-stat Ifn-i Signalingmentioning

confidence: 99%

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

Ning

2021

Viruses

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The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination- or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunotherapeutic strategies for immune diseases and cancers. Given their importance in antiviral immune response, viruses have evolved sophisticated immune escape strategies to subvert TRIM-mediated mechanisms. In this review, we focus on their regulation of IFN-I-mediated innate immune response, which plays key roles in antiviral and antitumor defense.

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Section: Trims In Regulating the Jak-stat Ifn-i Signalingmentioning

confidence: 99%

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

Ning

2021

Viruses

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“…Many proteome-wide studies performed in human cell lines have identified dyskerin as a target of SUMOylation, both by SUMO1 and SUMO2/3 (47)(48)(49)(50)(51)(52)(53)(54)(55). Compiling the results of these studies, it is evident that dyskerin is a highly decorated target for SUMOylation, with 24 sites identified by mass spectrometry (MS) analyses ( Figure 1A).…”

Section: The C-terminal Nuclear/nucleolar Localization Sequence Of Dymentioning

confidence: 68%

SUMOylation- and GAR1-dependent regulation of dyskerin nuclear and subnuclear localization

MacNeil

Lambert-Lanteigne

Qin

et al. 2020

Preprint

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SummaryDyskerin, a telomerase-associated protein and H/ACA ribonucleoprotein complex component plays an essential role in human telomerase assembly and activity. The nuclear and subnuclear compartmentalization of dyskerin and the H/ACA complex is an important though incompletely understood aspect of H/ACA ribonucleoprotein function. The posttranslational modification, SUMOylation, targets a wide variety of proteins, including numerous RNA-binding proteins, and most identified targets reported to date localize to the nucleus. Four SUMOylation sites were previously identified in the C-terminal Nuclear/Nucleolar Localization Signal (N/NoLS) of dyskerin, each located within one of two lysine-rich clusters. We found that a cytoplasmic localized C-terminal truncation variant of dyskerin lacking most of the C-terminal N/NoLS and both lysine-rich clusters represents an under-SUMOylated variant of dyskerin compared to wildtype dyskerin. We demonstrate that mimicking constitutive SUMOylation of dyskerin using a SUMO3-fusion construct can drive nuclear accumulation of this variant, and that the SUMO site K467 in this N/NoLS is particularly important for the subnuclear localization of dyskerin to the nucleolus in a mature H/ACA complex assembly- and SUMO-dependent manner. We also characterize a novel SUMO-interacting motif in the mature H/ACA complex component GAR1 that mediates the interaction between dyskerin and GAR1. Mislocalization of dyskerin, either in the cytoplasm or excluded from the nucleolus, disrupts dyskerin function and leads to reduced interaction of dyskerin with the telomerase RNA. These data indicate a role for dyskerin C-terminal N/NoLS SUMOylation in regulating the nuclear and subnuclear localization of dyskerin, which is essential for dyskerin function as both a telomerase-associated protein and as an H/ACA ribonucleoprotein involved in rRNA and snRNA biogenesis.

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“…We note that many of the reported SUMO-modified IFN-related host factors have not been identified as such in any of the large-scale unbiased SUMO proteomic experiments published to date [33][34][35][36][37][38], with the key exceptions of examples such as STAT1, PML and SAMHD1, as well as ADAR and PIAS1-4 [33][34][35][36][37][38]. Thus, there seems to be an unresolved discrepancy between results obtained from individual targeted studies and results obtained from global proteomic screens.…”

Section: Sumoylation Is a Key Regulator Of Innate Antiviral Immunitymentioning

confidence: 86%

“…The Chelbi-Alix group set out to identify specific IFNα-induced changes to SUMOylation using quantitative proteomics [34,35]. They used HEK293 cells stably expressing His6-SUMO3-Q87R-Q88N (see Section 3.2 and Figure 4D) [59] grown in SILAC medium, and treated them with IFNα for short (0.75 h) or long (16 h) periods of time, while mock treated cells were used as a negative control [35].…”

Section: Sumo Proteomics During the Ifn Responsementioning

confidence: 99%

Proteomic Approaches to Dissect Host SUMOylation during Innate Antiviral Immune Responses

Lork

Lieber

Hale

2021

Viruses

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SUMOylation is a highly dynamic ubiquitin-like post-translational modification that is essential for cells to respond to and resolve various genotoxic and proteotoxic stresses. Virus infections also constitute a considerable stress scenario for cells, and recent research has started to uncover the diverse roles of SUMOylation in regulating virus replication, not least by impacting antiviral defenses. Here, we review some of the key findings of this virus-host interplay, and discuss the increasingly important contribution that large-scale, unbiased, proteomic methodologies are making to discoveries in this field. We highlight the latest proteomic technologies that have been specifically developed to understand SUMOylation dynamics in response to cellular stresses, and comment on how these techniques might be best applied to dissect the biology of SUMOylation during innate immunity. Furthermore, we showcase a selection of studies that have already used SUMO proteomics to reveal novel aspects of host innate defense against viruses, such as functional cross-talk between SUMO proteins and other ubiquitin-like modifiers, viral antagonism of SUMO-modified antiviral restriction factors, and an infection-triggered SUMO-switch that releases endogenous retroelement RNAs to stimulate antiviral interferon responses. Future research in this area has the potential to provide new and diverse mechanistic insights into host immune defenses.

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Cross-talk between SUMOylation and ISGylation in response to interferon

Cited by 20 publications

References 59 publications

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

SUMOylation- and GAR1-dependent regulation of dyskerin nuclear and subnuclear localization

Proteomic Approaches to Dissect Host SUMOylation during Innate Antiviral Immune Responses

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