Disease relevance of ISG20

• In the absence of IFN treatment, ISG20-overexpressing HeLa cells showed resistance to infections by vesicular stomatitis virus (VSV), influenza virus, and encephalomyocarditis virus (three RNA genomic viruses) but not to the DNA genomic adenovirus [1].
• Altogether, these data reflect the ineffectiveness of virus replication in cells overexpressing ISG20 and demonstrate that ISG20 represents a new factor in the IFN-mediated antiviral barrier against HIV-1 [2].
• In this report, it was shown that ISG20 expression is rapidly and strongly induced during human immunodeficiency virus type 1 (HIV-1) infection [2].
• HEM45 mRNA was widely expressed at low levels in cell lines and was up regulated by E2 in ER-positive breast cancer lines [3].
• Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25 [4].

High impact information on ISG20

• Although inactive by itself, addition of annexin-1 to stimulated T cells augmented anti-CD3/CD28-mediated CD25 and CD69 expression and cell proliferation [5].
• Of importance, we demonstrate that different carcinoma entities associated with elevated levels of PGE2 coexpress CD25 and IDO in peritumoral dendritic cells, suggesting that PGE2 might influence IDO expression in human DCs in the tumor environment [6].
• While maturation of DCs induced IDO expression on transcriptional level, only integration of PGE2 signaling led to up-regulation of functional IDO protein as well as significant expression of cell-surface and soluble CD25 protein [6].
• Adult T-cell leukemia (ATL) consists of an overabundance of T cells, which express CD25 [4].
• In summary, (211)At-7G7/B6 could serve as an effective therapeutic agent for patients with CD25-expressing leukemias [7].

Biological context of ISG20

• Two families of transcription factors are implicated in the transcriptional activation of ISG20 by dsRNA [8].
• Assignment of ISG20 encoding a new interferon-induced PML nuclear body-associated protein, to chromosome 15q26 by in situ hybridization [9].
• In addition, it was demonstrated that the replication kinetics of an HIV-1-derived virus expressing the ISG20 protein (HIV-1(NL4-3ISG20)) was delayed in both CEM cells and peripheral blood mononuclear cells [2].
• Paradoxically, despite the antiviral activity of ISG20 protein, virus rescue observed in HIV-1(NL4-3ISG20)-infected cells was not due to mutation or partial deletion of the ISG20 transgene, suggesting that the virus was able to counteract the cellular defences [2].
• We also present evidences that ISG20 was associated with survival of motor neuron (SMN)-containing macromolecular nuclear complexes required for the biogenesis of various small nuclear ribonucleoproteins [10].

Anatomical context of ISG20

• This new gene is induced by both type I and II IFNs in various cell lines and will be referred to as ISG20 for interferon-stimulated gene product of 20 kDa [11].
• We correlated changes in gene expression and clinical/laboratory features of SLE and found that expression of ISG20, EPSTI1 and SLED1 are significantly correlated with lymphocyte counts [12].
• Expression and estrogen regulation of the HEM45 MRNA in human tumor lines and in the rat uterus [3].
• HEM45 mRNA expression in cultured cells was increased by estrogen in the presence of cycloheximide, indicating direct ER-regulation of HEM45 [3].
• OBJECTIVE: We sought to examine whether CD4(+) T cells bearing CD103 are suppressor cells, regardless of CD25 coexpression [13].

Associations of ISG20 with chemical compounds

• The human interferon- and estrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro [14].
• We have solved the crystal structure of human ISG20 complexed with two Mn2+ ions and uridine 5'-monophosphate (UMP) at 1.9 A resolution [15].
• However, ISG20 also has distinctive residues, Met14 and Arg53, to accommodate hydrogen bonds with the 2'-OH group of the UMP ribose, and these residues may be responsible for the preference of ISG20 for RNA substrates [15].
• Here, we extend these findings, demonstrating a concomitant induction of IDO and secretion of soluble CD25 after DC maturation in the presence of PGE2 [6].
• After atropine the CD25 was unchanged after placebo (2.3 +/- 0.3 micrograms) and atenolol (7.7 +/- 1.3 micrograms); it was reduced after propranolol (24.8 +/- 5.0 micrograms), but remained different from atenolol [16].

Other interactions of ISG20

• PML and two other NBs-associated proteins, Sp100 And ISG20 are directly induced by interferons (IFN) [17].
• ISG20, a new interferon-induced RNase specific for single-stranded RNA, defines an alternative antiviral pathway against RNA genomic viruses [1].
• We thus show that, besides RNase L, ISG20 has an antiviral activity, supporting the idea that it might represent a novel antiviral pathway in the mechanism of IFN action [1].
• We have recently isolated a new human IFN-induced gene that we have termed ISG20, which codes for a 3' to 5' exonuclease with specificity for single-stranded RNA and, to a lesser extent, for DNA [1].
• The NBs-associated proteins, PML, Sp100, Sp140, Sp110, ISG20 and PA28 are induced by IFN suggesting that nuclear bodies could play a role in IFN response [18].

Analytical, diagnostic and therapeutic context of ISG20

• In this report, using immunofluorescence analysis, we demonstrate that in addition to a diffuse cytoplasmic and nucleoplasmic localization, the endogenous ISG20 protein was present in the nucleus both in the nucleolus and in the Cajal bodies (CBs) [10].
• The levels of the rat uterine HEM45 sequence were elevated by estrogen 3 to 15 h after treatment [3].
• Ligation of CD80 Is Critical for High-Level CD25 Expression on CD8+ T Lymphocytes [19].
• However, there was no change in the amount of CD25 mRNA in T cells after coculture [20].
• The role of these cells in primary transplant recipients has been explored using anti-CD25 antibody but specific targeting of Treg is not possible since CD25 is also up-regulated on activated effector T cells [21].

References