ISG15

ISG15

A gene on chromosome 1p36.33 that encodes a ubiquitin-like protein which binds to target proteins in response to IFN-alpha or IFN-beta stimulation. ISG15 has chemotactic activity on neutrophils and activates them, triggering their release of eosinophil chemotactic factors. It may: play a role as a trans-acting binding factor, directing ligated target proteins to bind to intermediate filaments; have autocrine, paracrine and endocrine effects, including cell-to-cell signalling, possibly by inducing IFN-gamma secretion by macrophages; respond to IFN-tau secreted by the foetus; and bind and regulate proteins involved in the release of prostaglandin F2-alpha, preventing lysis of the corpus luteum and maintaining the pregnancy.
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The importance of eIF4E2 (aka 4EHP in metazoan and nCBP in plants) in viral infection has been shown only indirectly in that modification of eIF4E2 by covalent addition of interferon-stimulated gene (ISG15) (ISGylation) results in binding to the 5'-cap with greater affinity than the unmodified protein (Okumura et al.
[88] A dose-dependent induction of peripheral interferon-stimulated gene 15 (ISG15) gene expression has been observed, but without a clinically significant change in HBsAg concentrations.
Chung et al., "IFN-A4 potently blocks IFN-a signalling by ISG15 and USP18 in hepatitis C virus infection," Scientific Reports, vol.
In resting macrophages, knockdown of lincRNA-Cox2 leads to increased expression of more than 700 genes, including a number of chemokines (CCL5, CX3CL1), chemokine receptors (CCRl), and interferon-stimulated genes (ISGs) (IRF7, OAS1a, OaS1l, OAS2, IFI204, and ISG15).
Selvaggi et al., "ISG15 expression correlates with HIV-1 viral load and with factors regulating T cell response," Immunobiology, vol.
Mendelian Susceptibility to Mycobacterial Diseases MSMD has especially been associated with defects in the IL12B, IL12RB1, IRF8, ISG15, NEMO, IFNGR1, IFNGR2, STAT1, IRF8, and CYBB genes (15-22).
The baseline expression levels of 25 IFN-regulated genes (MxA, GPR3, IL17RC, ISG15, TRAIL, OASL, IFIT1, IFIT2, RSAD2, OAS3, IFI44L, TRIM22, IL10, CXCL10, STAT1, OAS1, OAS2, IFNAR1, IFNAR2, IFN[beta], ISG20, IFI6, PKR, IRF7, and USP18) were examined but were not confirmed to have predictive value [53].
During interferon, genotoxic stress, and pathogen infection, the ubiquitin-like molecule ISG15 is covalently added to eIF4E2 to increase its capbinding affinity [48].
The first cluster contained interferon-stimulated gene 15 (ISG15), which is a biomarker for predicting sensitivity to irinotecan, an anticancer drug and topoisomerase I inhibitor (Figure 2(a)).
Genetic disorders associated with inborn errors in IFN-[gamma]-dependent immunity include those which impair production of IFN-[gamma] (IL12B, IL12RB1, IRF8, ISG15, NEMO) and those which impair response to IFN-[gamma] (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) [2].
vOTU has broad deubiquinating activity and is able to cleave the ubiquitin-like interferon-stimulated gene protein (ISG15) involved in host immune regulation, particularly the NF-[kappa]B (nuclear factor kappa light chain enhancer of activated B cells) signaling pathway (24-26).