ISG15 ubiquitin like modifier
Gene Context Sentence
Table 2. Analysis of context sentence of ISG15 gene in 15 abstracts.
|Gene Context Sentence
|Here, the biochemical activity of SARS-CoV-2 PLpro against ubiquitin and ISG15 substrates is evaluated revealing that the protease has a marked reduction in its ability to process K48 linked Ub substrates compared to its counter part in SARS-CoV. […] Additionally, its substrate activity more closely mirrors that of the PLpro from the Middle East respiratory syndrome coronavirus and prefers ISG15s from certain species including humans.
|Both deubiquitinating and deISGylating functions involve the removal of the small regulatory polypeptides, ubiquitin and ISG15, respectively, from target proteins. […] ISG15 is a ubiquitin-like modifier with pleiotropic effects, typically expressed during the host cell immune response.
|ISG15 is a ubiquitin-like modifier that also functions extracellularly, signaling through the LFA-1 integrin to promote interferon (IFN)-γ release from natural killer (NK) and T cells. […] The signals that lead to the production of extracellular ISG15 and the relationship between its two core functions remain unclear. […] We show that both epithelial cells and lymphocytes can secrete ISG15, which then signals in either an autocrine or paracrine manner to LFA-1-expressing cells. […] Microbial pathogens and Toll-like receptor (TLR) agonists result in both IFN-β-dependent and -independent secretion of ISG15, and residues required for ISG15 secretion are mapped. […] Intracellular ISGylation inhibits secretion, and viral effector proteins, influenza B NS1, and viral de-ISGylases, including SARS-CoV-2 PLpro, have opposing effects on secretion of ISG15. […] These results establish extracellular ISG15 as a cytokine-like protein that bridges early innate and IFN-γ-dependent immune responses, and indicate that pathogens have evolved to differentially inhibit the intracellular and extracellular functions of ISG15.
|These ISGs (IFIT1, IFITM1, IRF7, ISG15, MX1, and OAS2) can be considered as potential candidates for drug targets in the treatments of COVID-19.
|In primary peripheral blood mononuclear cells from the patients, downstream type I interferon (IFN) signaling was transcriptionally downregulated, as measured by significantly decreased mRNA expression of IRF7, IFNB1, and ISG15 on stimulation with the TLR7 agonist imiquimod as compared with family members and controls.
|SCoV2-PLpro and SCoV-PLpro share 83% sequence identity but exhibit different host substrate preferences; SCoV2-PLpro preferentially cleaves the ubiquitin-like interferon-stimulated gene 15 protein (ISG15), whereas SCoV-PLpro predominantly targets ubiquitin chains. […] The crystal structure of SCoV2-PLpro in complex with ISG15 reveals distinctive interactions with the amino-terminal ubiquitin-like domain of ISG15, highlighting the high affinity and specificity of these interactions. […] Furthermore, upon infection, SCoV2-PLpro contributes to the cleavage of ISG15 from interferon responsive factor 3 (IRF3) and attenuates type I interferon responses.
|We have identified 4 DEGs-Isg15, Ddx58, Oasl1, Usp18 by analyzing a mRNA GEO dataset.
|The SARS-CoV-2 coronavirus encodes an essential papain-like protease domain as part of its non-structural protein (nsp)-3, namely SARS2 PLpro, that cleaves the viral polyprotein, but also removes ubiquitin-like ISG15 protein modifications as well as, with lower activity, Lys48-linked polyubiquitin. […] Structures of PLpro bound to ubiquitin and ISG15 reveal that the S1 ubiquitin-binding site is responsible for high ISG15 activity, while the S2 binding site provides Lys48 chain specificity and cleavage efficiency.
|No correlation was found with other molecules associated with Coronavirus infection, including ADAR, BST2, IRF3, IFITM3, ISG15, MX1, MX2, RNASEL, RSAD2, and VPRBP.
|Then, we conducted fluorescent resonance energy transfer-based protease assays and found that PDCoV PLpro can cleave a peptide by mimicking the cognate nsp2/nsp3 cleavage site in peptide substrates and exhibits deubiquitinating and de-interferon stimulated gene(deISGylating) activities by hydrolysing ubiquitin-7-amino-4-methylcoumarin (Ub-AMC) and ISG15-AMC substrates.
|Moreover, we sought to understand the interplay of type I interferon (IFN-I) with ACE2, furin and TMPRSS2 by evaluating their gene expression with respect to ISG15, a well-known marker of IFN activation, in upper respiratory samples and after ex vivo IFNβ exposure. […] Moreover, there was a strong positive correlation between ISG15 and ACE2 levels.
|NMR data indicate that GRL0617 blocks the binding of ISG15 C-terminus to PLpro. […] Using truncated ISG15 mutants, we show that the C-terminus of ISG15 plays a dominant role in binding PLpro. […] Structural analysis reveals that the ISG15 C-terminus binding pocket in PLpro contributes a disproportionately large portion of binding energy, thus this pocket is a hot spot for antiviral drug discovery targeting PLpro.
|In order to assess the in vivo relationship between ACE2 and furin expression and the IFN response in nasopharyngeal cells, we first examined ACE2 and furin levels and their correlation with the well-known marker of IFNs’ activation, ISG15, in children (n = 59) and adults (n = 48), during respiratory diseases not caused by SARS-CoV-2. […] A strong positive correlation was found between ACE2 expression, but not of furin, and ISG15 in all patients analyzed.
|In this review, we present the current knowledge of immune evasion by viral pathogens that manipulate ubiquitin- or ISG15-dependent mechanisms of RLR activation. […] Finally, we discuss the possibility of targeting virally-encoded proteins that manipulate ubiquitin- or ISG15-mediated innate immune responses for the development of new antivirals and vaccines.
|In total, ten genes (CBL, ISG15, NEDD4, PML, REL, CTNNB1, ERBB2, JUN, RPS8 and STUB1) were identified as good diagnostic biomarkers.