Crosstalk Between SUMO and Ubiquitin-Like Proteins: Implication for Antiviral Defense

Chelbi-Alix, Mounira K.; Thibault, Pierre

doi:10.3389/fcell.2021.671067

Cited by 17 publications

(19 citation statements)

References 238 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that SUMOylation are closely related to cancer initiation and progression ( Xie et al, 2020 ). There is a crosstalk between ubiquitination and SUMOylation in cells ( Chelbi-Alix and Thibault, 2021 ), and SUMOylation plays a significant role in maintaining genomic stability via SUMO-targeted ubiquitin ligase (STUbL) ( Nie and Boddy, 2016 ). Interestingly, we also found a significant change of ubiquitination pathway when we performed KEGG enrichment analysis of all down-regulated phosphorylation in CRC cells versus the normal cells ( Supplementary Figure S2 ).…”

Section: Resultsmentioning

confidence: 99%

Multi-Platform-Based Analysis Characterizes Molecular Alterations of the Nucleus in Human Colorectal Cancer

Zhang

Wu²,

Gao³

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Background: The disturbed molecular alterations of nucleus may promote the development of colorectal cancer (CRC). A multi-platform-based analysis of nucleus of CRC patients helps us to better understand the underlying mechanism of CRC and screen out the potential drug targets for clinical treatment. However, such studies on nucleus in human CRC are still lacking.Methods: We collected the cancerous and para-cancerous tissues from eight CRC patients and performed a multiplex analysis of the molecular changes of the nucleus, including structural variations (SVs), DNA methylation, chromatin accessibility, proteome and phosphorproteome.Results: In our study, we revealed a significant molecular change of nucleus of CRC patients using our original proteomic and phosphorylomic datasets. Subsequently, we characterized the molecular alterations of nucleus of CRC patients at multiple dimensionalities, including DNA, mRNA, protein and epigenetic modification. Next, we found that the great molecular changes of nucleus might affect the biological processes named endocytosis and ubiquitin-mediated proteolysis. Besides, we identified DYNC1LI2 and TPR as the potentially hub proteins within the network of nuclear genes in CRC cells. Furthermore, we identified 1905 CRC-specific SVs, and proclaimed 17 CRC-specific SVs were probably associated with the disturbance of immune microenvironment of CRC patients. We also revealed that the SVs of CXCL5, CXCL10 and CXCL11 might be the core SVs among all the immune-relevant SVs. Finally, we identified seven genes as the upstream transcriptional factors potentially regulating the expression of nuclear genes, such as YY1 and JUN, using a multi-omics approach.Conclusion: Here, we characterized the molecular changes of nucleus of CRC patients, disclosed the potentially core nuclear genes within the network, and identified the probable upstream regulator of nucleus. The findings of this study are helpful to understand the pathogenic molecular changes of nucleus in CRC patients and provide a functional context for drug development in future.

show abstract

Section: Resultsmentioning

confidence: 99%

Multi-Platform-Based Analysis Characterizes Molecular Alterations of the Nucleus in Human Colorectal Cancer

Zhang

Wu²,

Gao³

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Several mechanisms have been demonstrated through which free ISG15 and ISGylation possibly contribute to the etiology of human ailments. ISG15 is involved through marking proteins for degradation, antagonizing protein degradation (stabilizing proteins), affecting protein localization, preventing the formation of protein complexes, or regulating immune response(s) [96,126,[136][137][138][139][140][141][142][143][144][145][146][147][148][149][150]. In the current review, we shall focus on the role of the ISG15 pathway in human diseases through protein degradation.…”

Section: The Isg15 Pathway In Human Diseasesmentioning

confidence: 99%

ISG15 and ISGylation in Human Diseases

Mirzalieva

Juncker

Schwartzenburg

et al. 2022

Cells

View full text Add to dashboard Cite

Type I Interferons (IFNs) induce the expression of >500 genes, which are collectively called ISGs (IFN-stimulated genes). One of the earliest ISGs induced by IFNs is ISG15 (Interferon-Stimulated Gene 15). Free ISG15 protein synthesized from the ISG15 gene is post‑translationally conjugated to cellular proteins and is also secreted by cells into the extracellular milieu. ISG15 comprises two ubiquitin-like domains (UBL1 and UBL2), each of which bears a striking similarity to ubiquitin, accounting for its earlier name ubiquitin cross-reactive protein (UCRP). Like ubiquitin, ISG15 harbors a characteristic β‑grasp fold in both UBL domains. UBL2 domain has a conserved C‑terminal Gly-Gly motif through which cellular proteins are appended via an enzymatic cascade similar to ubiquitylation called ISGylation. ISG15 protein is minimally expressed under physiological conditions. However, its IFN‑dependent expression is aberrantly elevated or compromised in various human diseases, including multiple types of cancer, neurodegenerative disorders (Ataxia Telangiectasia and Amyotrophic Lateral Sclerosis), inflammatory diseases (Mendelian Susceptibility to Mycobacterial Disease (MSMD), bacteriopathy and viropathy), and in the lumbar spinal cords of veterans exposed to Traumatic Brain Injury (TBI). ISG15 and ISGylation have both inhibitory and/or stimulatory roles in the etiology and pathogenesis of human diseases. Thus, ISG15 is considered a “double-edged sword” for human diseases in which its expression is elevated. Because of the roles of ISG15 and ISGylation in cancer cell proliferation, migration, and metastasis, conferring anti-cancer drug sensitivity to tumor cells, and its elevated expression in cancer, neurodegenerative disorders, and veterans exposed to TBI, both ISG15 and ISGylation are now considered diagnostic/prognostic biomarkers and therapeutic targets for these ailments. In the current review, we shall cover the exciting journey of ISG15, spanning three decades from the bench to the bedside.

show abstract

“…[ 124 ] SUMOylation also plays an important role downstream of IFN antiviral defense, which has recently been the focus of a large amount of work. [ 125 , 126 ]…”

Section: Sumoylation Is a Vital Regulator Of Antiviral Innate And Int...mentioning

confidence: 99%

SUMOylation in Viral Replication and Antiviral Defense

Fan

Zhang

et al. 2022

Advanced Science

View full text Add to dashboard Cite

SUMOylation is a ubiquitination-like post-translational modification that plays an essential role in the regulation of protein function. Recent studies have shown that proteins from both RNA and DNA virus families can be modified by SUMO conjugation, which facilitates viral replication. Viruses can manipulate the entire process of SUMOylation through interplay with the SUMO pathway. By contrast, SUMOylation can eliminate viral infection by regulating host antiviral immune components. A deeper understanding of how SUMOylation regulates viral proteins and cellular antiviral components is necessary for the development of effective antiviral therapies. In the present review, the regulatory mechanism of SUMOylation in viral replication and infection and the antiviral immune response, and the consequences of this regulation for viral replication and engagement with antiviral innate immunity are summarized. The potential therapeutic applications of SUMOylation in diseases caused by viruses are also discussed.

show abstract

Crosstalk Between SUMO and Ubiquitin-Like Proteins: Implication for Antiviral Defense

Cited by 17 publications

References 238 publications

Multi-Platform-Based Analysis Characterizes Molecular Alterations of the Nucleus in Human Colorectal Cancer

Multi-Platform-Based Analysis Characterizes Molecular Alterations of the Nucleus in Human Colorectal Cancer

ISG15 and ISGylation in Human Diseases

SUMOylation in Viral Replication and Antiviral Defense

Contact Info

Product

Resources

About