Isg15

Summary

Gene Symbol: Isg15
Description: ISG15 ubiquitin-like modifier
Alias: G1p2, IGI15, IP17, Irfp, UCRP, ubiquitin-like protein ISG15, interferon, alpha-inducible protein, interferon-induced 15 kDa protein, interferon-induced 15-KDa protein, interferon-induced 17 kDa protein, interferon-stimulated protein (15 kDa), interferon-stimulated protein 15, ubiquitin cross-reactive protein
Species: mouse
Products:     Isg15

Top Publications

  1. Austin K, Bany B, Belden E, Rempel L, Cross J, Hansen T. Interferon-stimulated gene-15 (Isg15) expression is up-regulated in the mouse uterus in response to the implanting conceptus. Endocrinology. 2003;144:3107-13 pubmed
    ..to pregnancy is induction of an interferon (IFN)-stimulated gene (ISG) that encodes the ubiquitin-related protein, ISG15. Because the mode of implantation differs among species, we tested whether Isg15 mRNA was also expressed in the ..
  2. Lu G, Reinert J, Pitha Rowe I, Okumura A, Kellum M, Knobeloch K, et al. ISG15 enhances the innate antiviral response by inhibition of IRF-3 degradation. Cell Mol Biol (Noisy-le-grand). 2006;52:29-41 pubmed
    ..treatment and NDV infection profoundly increase conjugation of interferon induced ubiquitin- like protein ISG15 to cellular proteins. ISGylated IRF-3 could be detected both in interferon treated and virus-infected cells...
  3. Liu M, Reimschuessel R, Hassel B. Molecular cloning of the fish interferon stimulated gene, 15 kDa (ISG15) orthologue: a ubiquitin-like gene induced by nephrotoxic damage. Gene. 2002;298:129-39 pubmed
    ..Sequence analysis revealed that 40.1 contains tandem UBL domains, and shares homology with ISG15, a 15 kD interferon-(IFN) stimulated UBL found in mammals...
  4. Versteeg G, Hale B, van Boheemen S, Wolff T, Lenschow D, Garcia Sastre A. Species-specific antagonism of host ISGylation by the influenza B virus NS1 protein. J Virol. 2010;84:5423-30 pubmed publisher
    Interferon-stimulated expression and conjugation of the ubiquitin-like modifier ISG15 restricts replication of several viruses...
  5. Skaug B, Chen Z. Emerging role of ISG15 in antiviral immunity. Cell. 2010;143:187-90 pubmed publisher
    Cells express a plethora of interferon-stimulated genes (ISGs) in response to viral infection. Among these is ISG15, a ubiquitin-like protein (UBL) that can be covalently attached to both host and viral proteins...
  6. Lai C, Struckhoff J, Schneider J, Martinez Sobrido L, Wolff T, Garcia Sastre A, et al. Mice lacking the ISG15 E1 enzyme UbE1L demonstrate increased susceptibility to both mouse-adapted and non-mouse-adapted influenza B virus infection. J Virol. 2009;83:1147-51 pubmed publisher
    b>ISG15 functions as a critical antiviral molecule against influenza virus, with infection inducing both the conjugation of ISG15 to target proteins and production of free ISG15...
  7. Hamerman J, Hayashi F, Schroeder L, Gygi S, Haas A, Hampson L, et al. Serpin 2a is induced in activated macrophages and conjugates to a ubiquitin homolog. J Immunol. 2002;168:2415-23 pubmed
    ..We also demonstrate here that a ubiquitin homolog, IFN-stimulated gene of 15-kDa (ISG15), is strongly induced during in vitro and in vivo activation of macrophages and that it conjugates to spi2a in ..
  8. Werneke S, Schilte C, Rohatgi A, Monte K, Michault A, Arenzana Seisdedos F, et al. ISG15 is critical in the control of Chikungunya virus infection independent of UbE1L mediated conjugation. PLoS Pathog. 2011;7:e1002322 pubmed publisher
    ..To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly ..
  9. Knobeloch K, Utermöhlen O, Kisser A, Prinz M, Horak I. Reexamination of the role of ubiquitin-like modifier ISG15 in the phenotype of UBP43-deficient mice. Mol Cell Biol. 2005;25:11030-4 pubmed
    UBP43/USP18 was described as a specific protease that removes conjugated ubiquitin-like modifier ISG15 from target proteins...

More Information

Publications68

  1. Giannakopoulos N, Luo J, Papov V, Zou W, Lenschow D, Jacobs B, et al. Proteomic identification of proteins conjugated to ISG15 in mouse and human cells. Biochem Biophys Res Commun. 2005;336:496-506 pubmed
    Though the interferon-inducible protein ISG15 was one of the first ubiquitin-like modifiers to be discovered, much remains unknown about the identity of proteins conjugated to ISG15 or the biologic consequences of modification...
  2. Hemelaar J, Borodovsky A, Kessler B, Reverter D, Cook J, Kolli N, et al. Specific and covalent targeting of conjugating and deconjugating enzymes of ubiquitin-like proteins. Mol Cell Biol. 2004;24:84-95 pubmed
    ..To target and identify UBL-modifying enzymes, we produced Nedd8, ISG15, and SUMO-1 in Escherichia coli and equipped them with a C-terminal electrophilic trap (vinyl sulfone [VS]) via an ..
  3. Kim K, Giannakopoulos N, Virgin H, Zhang D. Interferon-inducible ubiquitin E2, Ubc8, is a conjugating enzyme for protein ISGylation. Mol Cell Biol. 2004;24:9592-600 pubmed
    ..Here, we report the identification of an ISG15-conjugating enzyme, Ubc8...
  4. Owhashi M, Taoka Y, Ishii K, Nakazawa S, Uemura H, Kambara H. Identification of a ubiquitin family protein as a novel neutrophil chemotactic factor. Biochem Biophys Res Commun. 2003;309:533-9 pubmed
    ..amino acid sequences and MALDI-TOF mass analysis of IP17 revealed that IP17 is identical to a murine homologue of ISG15/UCRP, a member of the ubiquitin family of proteins that are inducible by interferon-beta...
  5. Malakhov M, Kim K, Malakhova O, Jacobs B, Borden E, Zhang D. High-throughput immunoblotting. Ubiquitiin-like protein ISG15 modifies key regulators of signal transduction. J Biol Chem. 2003;278:16608-13 pubmed
    b>ISG15 is a ubiquitin-like protein that conjugates to numerous proteins in cells treated with interferon or lipopolysaccharide...
  6. Malakhova O, Malakhov M, Hetherington C, Zhang D. Lipopolysaccharide activates the expression of ISG15-specific protease UBP43 via interferon regulatory factor 3. J Biol Chem. 2002;277:14703-11 pubmed
    UBP43 is a protease that specifically removes a ubiquitin-like protein, ISG15, from its targets. Highest levels of UBP43 expression are detected in macrophages and in cell lines of monocytic lineage...
  7. Bogunovic D, Byun M, Durfee L, Abhyankar A, Sanal O, Mansouri D, et al. Mycobacterial disease and impaired IFN-? immunity in humans with inherited ISG15 deficiency. Science. 2012;337:1684-8 pubmed
    b>ISG15 is an interferon (IFN)-?/?-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice...
  8. Kim M, Yoo J. Inhibition of hepatitis C virus replication by IFN-mediated ISGylation of HCV-NS5A. J Immunol. 2010;185:4311-8 pubmed publisher
    b>ISG15 is a ubiquitin-like molecule whose expression is induced by type I IFN (IFN-?/?) or in response to virus or bacterial infection...
  9. Tang Y, Zhong G, Zhu L, Liu X, Shan Y, Feng H, et al. Herc5 attenuates influenza A virus by catalyzing ISGylation of viral NS1 protein. J Immunol. 2010;184:5777-90 pubmed publisher
    Ubiquitin-like protein ISG15, which is robustly induced by IFN or virus, is implicated to inhibit influenza A virus (IAV) in vivo. But the underlying mechanism still remains largely unknown...
  10. Okumura F, Okumura A, Uematsu K, Hatakeyama S, Zhang D, Kamura T. Activation of double-stranded RNA-activated protein kinase (PKR) by interferon-stimulated gene 15 (ISG15) modification down-regulates protein translation. J Biol Chem. 2013;288:2839-47 pubmed publisher
    The ubiquitin-like molecule ISG15 (UCRP) and protein modification by ISG15 (ISGylation) are strongly induced by interferon, genotoxic stress, and pathogen infection, suggesting that ISG15 plays an important role in innate immune ..
  11. Lenschow D, Lai C, Frias Staheli N, Giannakopoulos N, Lutz A, Wolff T, et al. IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. Proc Natl Acad Sci U S A. 2007;104:1371-6 pubmed
    ..Yet, additional antiviral ISGs likely exist. IFN-stimulated gene 15 (ISG15) is a ubiquitin homolog that is rapidly up-regulated after viral infection, and it conjugates to a wide array of ..
  12. Ritchie K, Malakhov M, Hetherington C, Zhou L, Little M, Malakhova O, et al. Dysregulation of protein modification by ISG15 results in brain cell injury. Genes Dev. 2002;16:2207-12 pubmed
    UBP43 (USP18) is a protease that removes the ubiquitin-like modifier ISG15 from conjugated proteins. Here we present the first report of dysregulation of protein ISG15 modification by the generation of UBP43 knockout mice...
  13. Malakhova O, Kim K, Luo J, Zou W, Kumar K, Fuchs S, et al. UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity. EMBO J. 2006;25:2358-67 pubmed
    ..Lack of Ubp43, an IFN-inducible ISG15 deconjugating enzyme, leads to IFN hypersensitivity in ubp43-/- mice, suggesting an important function of Ubp43 in ..
  14. Lenschow D, Giannakopoulos N, Gunn L, Johnston C, O Guin A, Schmidt R, et al. Identification of interferon-stimulated gene 15 as an antiviral molecule during Sindbis virus infection in vivo. J Virol. 2005;79:13974-83 pubmed
    ..Using this approach, we identified a ubiquitin homolog, interferon-stimulated gene 15 (ISG15), as having antiviral activity...
  15. Osiak A, Utermöhlen O, Niendorf S, Horak I, Knobeloch K. ISG15, an interferon-stimulated ubiquitin-like protein, is not essential for STAT1 signaling and responses against vesicular stomatitis and lymphocytic choriomeningitis virus. Mol Cell Biol. 2005;25:6338-45 pubmed
    b>ISG15 is an interferon-induced ubiquitin-like modifier which can be conjugated to distinct, but largely unknown, proteins...
  16. Kim J, Luo J, Zhang D. The level of hepatitis B virus replication is not affected by protein ISG15 modification but is reduced by inhibition of UBP43 (USP18) expression. J Immunol. 2008;181:6467-72 pubmed
    ..UBP43 (USP18) is known as an ISG15-deconjugating enzyme and an inhibitor of type I IFN signaling independent of its enzyme activity...
  17. Malakhov M, Malakhova O, Kim K, Ritchie K, Zhang D. UBP43 (USP18) specifically removes ISG15 from conjugated proteins. J Biol Chem. 2002;277:9976-81 pubmed
    ..was undetectable in vitro directing us to investigate the possibility of Ub-like proteins such as SUMO, Nedd8, and ISG15 as probable substrates...
  18. Lee A, Chen B, Chew M, Barra N, Shenouda M, Nham T, et al. Inflammatory monocytes require type I interferon receptor signaling to activate NK cells via IL-18 during a mucosal viral infection. J Exp Med. 2017;214:1153-1167 pubmed publisher
    ..This study highlights the importance of type I IFN signaling in inflammatory monocytes and the induction of the early innate antiviral response. ..
  19. Kimmey J, Campbell J, Weiss L, Monte K, Lenschow D, Stallings C. The impact of ISGylation during Mycobacterium tuberculosis infection in mice. Microbes Infect. 2017;19:249-258 pubmed publisher
    ..tuberculosis remains uncertain. ISG15 is one of the most highly induced interferon stimulated genes (ISGs) during M. tuberculosis infection...
  20. Wood L, Sankar S, Reed R, Haas A, Liu L, MCKINNON P, et al. A novel role for ATM in regulating proteasome-mediated protein degradation through suppression of the ISG15 conjugation pathway. PLoS ONE. 2011;6:e16422 pubmed publisher
    ..to its role in DNA repair, ATM also regulates proteasome-mediated protein turnover through suppression of the ISG15 pathway...
  21. Henkes L, Pru J, Ashley R, Anthony R, Veeramachaneni D, Gates K, et al. Embryo mortality in Isg15-/- mice is exacerbated by environmental stress. Biol Reprod. 2015;92:36 pubmed publisher
    The interferon-stimulated gene 15 (Isg15) encodes a ubiquitin-like protein that is induced in the endometrium by pregnancy in mice, humans, and ruminants...
  22. Dai J, Pan W, Wang P. ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro. Virol J. 2011;8:468 pubmed publisher
    ..Vaccines against these two flaviviruses are currently unavailable. Interferon- Stimulated Gene 15 (ISG15), encoding an ubiquitin-like protein, is significantly induced by type I interferons or viral infections...
  23. Yoshikawa A, Imagawa A, Nakata S, Fukui K, Kuroda Y, Miyata Y, et al. Interferon stimulated gene 15 has an anti-apoptotic effect on MIN6 cells. Endocr J. 2014;61:883-90 pubmed
    ..We used the mouse beta cell line MIN6 to investigate the role of ISG15 and paid special attention to apoptosis...
  24. Maragno A, Pironin M, Alcalde H, Cong X, Knobeloch K, Tangy F, et al. ISG15 modulates development of the erythroid lineage. PLoS ONE. 2011;6:e26068 pubmed publisher
    ..In a search for genes that are up-regulated during this differentiation process, we have identified ISG15 as being induced during late erythroid differentiation...
  25. Rodriguez M, Monte K, Thackray L, Lenschow D. ISG15 functions as an interferon-mediated antiviral effector early in the murine norovirus life cycle. J Virol. 2014;88:9277-86 pubmed publisher
    ..dendritic cells, macrophages, and mice deficient in free and conjugated forms of interferon-stimulated gene 15 (ISG15) revealed that ISG15 conjugation contributes to protection against MNV-1 both in vitro and in vivo...
  26. Basters A, Geurink P, Röcker A, Witting K, Tadayon R, Hess S, et al. Structural basis of the specificity of USP18 toward ISG15. Nat Struct Mol Biol. 2017;24:270-278 pubmed publisher
    ..USP) family, USP18 shows no reactivity toward ubiquitin but specifically deconjugates the interferon-induced Ubl ISG15. To identify the molecular determinants of this specificity, we solved the crystal structures of mouse USP18 alone ..
  27. Rahnefeld A, Klingel K, Schuermann A, Diny N, Althof N, Lindner A, et al. Ubiquitin-like protein ISG15 (interferon-stimulated gene of 15 kDa) in host defense against heart failure in a mouse model of virus-induced cardiomyopathy. Circulation. 2014;130:1589-600 pubmed publisher
    ..Here, we investigated the role of the ubiquitin-like modifier interferon-stimulated gene of 15 kDa (ISG15) in the pathogenesis of viral cardiomyopathy...
  28. Rossi J, Todd T, Daniels Z, Bazan N, Belayev L. Interferon-Stimulated Gene 15 Upregulation Precedes the Development of Blood-Brain Barrier Disruption and Cerebral Edema after Traumatic Brain Injury in Young Mice. J Neurotrauma. 2015;32:1101-8 pubmed publisher
    ..Interferon-stimulated gene 15 (ISG15) is upregulated after cerebral ischemia and is neuroprotective...
  29. Radoshevich L, Impens F, Ribet D, Quereda J, Nam Tham T, Nahori M, et al. ISG15 counteracts Listeria monocytogenes infection. elife. 2015;4: pubmed publisher
    b>ISG15 is an interferon-stimulated, linear di-ubiquitin-like protein, with anti-viral activity. The role of ISG15 during bacterial infection remains elusive...
  30. Gao D, Li T, Li X, Chen X, Li Q, Wight Carter M, et al. Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases. Proc Natl Acad Sci U S A. 2015;112:E5699-705 pubmed publisher
  31. Ketscher L, Basters A, Prinz M, Knobeloch K. mHERC6 is the essential ISG15 E3 ligase in the murine system. Biochem Biophys Res Commun. 2012;417:135-40 pubmed publisher
    ..Interferon-stimulated gene 15 (ISG15) is an UBL, which is strongly induced by type I Interferon and ISG15 modification was shown to play an essential ..
  32. Vargas Inchaustegui D, Xin L, Soong L. Leishmania braziliensis infection induces dendritic cell activation, ISG15 transcription, and the generation of protective immune responses. J Immunol. 2008;180:7537-45 pubmed
    ..braziliensis infection triggered transcription and phosphorylation of STAT molecules and IFN-stimulated gene 15 (ISG15)...
  33. Rempel L, Austin K, Ritchie K, Yan M, Shen M, Zhang D, et al. Ubp43 gene expression is required for normal Isg15 expression and fetal development. Reprod Biol Endocrinol. 2007;5:13 pubmed
    b>Isg15 covalently modifies murine endometrial proteins in response to early pregnancy. Isg15 can also be severed from targeted proteins by a specific protease called Ubp43 (Usp18)...
  34. Basters A, Geurink P, El Oualid F, Ketscher L, Casutt M, Krause E, et al. Molecular characterization of ubiquitin-specific protease 18 reveals substrate specificity for interferon-stimulated gene 15. FEBS J. 2014;281:1918-28 pubmed publisher
    Protein modification by interferon-stimulated gene 15 (ISG15), an ubiquitin-like modifier, affects multiple cellular functions and represents one of the major antiviral effector systems...
  35. Ketscher L, Hannß R, Morales D, Basters A, Guerra S, Goldmann T, et al. Selective inactivation of USP18 isopeptidase activity in vivo enhances ISG15 conjugation and viral resistance. Proc Natl Acad Sci U S A. 2015;112:1577-82 pubmed publisher
    Protein modification by the ubiquitin-like protein ISG15 is an interferon (IFN) effector system, which plays a major role in antiviral defense...
  36. Ashley R, Henkes L, Bouma G, Pru J, Hansen T. Deletion of the Isg15 gene results in up-regulation of decidual cell survival genes and down-regulation of adhesion genes: implication for regulation by IL-1beta. Endocrinology. 2010;151:4527-36 pubmed publisher
    The ubiquitin homolog interferon stimulated gene 15 (ISG15) is up-regulated in the endometrium in response to pregnancy in primates, ruminants, pigs, and mice...
  37. Ketscher L, Knobeloch K. ISG15 uncut: Dissecting enzymatic and non-enzymatic functions of USP18 in vivo. Cytokine. 2015;76:569-571 pubmed publisher
    Posttranslational protein modification by ISG15 plays an important role in antiviral defense. We selectively inactivated the ISG15 isopeptidase activity of USP18 in mice...
  38. Brown A, Simmen R, Raj V, Van T, MacLeod S, Simmen F. Krüppel-like factor 9 (KLF9) prevents colorectal cancer through inhibition of interferon-related signaling. Carcinogenesis. 2015;36:946-55 pubmed publisher
    ..Circulating levels of the cytokine, interferon-stimulated gene 15 (ISG15) were increased in Apc(Min/+)/Klf9(+/-) and Apc(Min/+)/Klf9(-/-) mice relative to Apc(Min/+)/Klf9(+/+)...
  39. Dauphinee S, Richer E, Eva M, McIntosh F, Paquet M, Dangoor D, et al. Contribution of increased ISG15, ISGylation and deregulated type I IFN signaling in Usp18 mutant mice during the course of bacterial infections. Genes Immun. 2014;15:282-92 pubmed publisher
    ..USP18 functions to regulate type I interferon (IFN) signaling and as a protease to remove ISG15 from substrate proteins...
  40. Villarroya Beltri C, Baixauli F, Mittelbrunn M, Fernandez Delgado I, Torralba D, Moreno Gonzalo O, et al. ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins. Nat Commun. 2016;7:13588 pubmed publisher
    ..ISGylation induction decreases MVB numbers and impairs exosome secretion. Using ISG15-knockout mice and mice expressing the enzymatically inactive form of the de-ISGylase USP18, we demonstrate in ..
  41. Kaur S, Lal L, Sassano A, Majchrzak Kita B, Srikanth M, Baker D, et al. Regulatory effects of mammalian target of rapamycin-activated pathways in type I and II interferon signaling. J Biol Chem. 2007;282:1757-68 pubmed
    ..We also demonstrate that the induction of key IFNalpha- or IFNgamma-inducible proteins (ISG15 (interferon-stimulated gene 15) and CXCL10) that mediate IFN responses are enhanced in 4E-BP1 (4E-BP1(-/-)) ..
  42. Wood L, Pan Z, Seavey M, Muthukumaran G, Paterson Y. The ubiquitin-like protein, ISG15, is a novel tumor-associated antigen for cancer immunotherapy. Cancer Immunol Immunother. 2012;61:689-700 pubmed publisher
    ..Recently, several studies have identified ISG15 as a molecule highly expressed in numerous malignancies...
  43. Morales D, Monte K, Sun L, Struckhoff J, Agapov E, Holtzman M, et al. Novel mode of ISG15-mediated protection against influenza A virus and Sendai virus in mice. J Virol. 2015;89:337-49 pubmed publisher
    b>ISG15 is a diubiquitin-like modifier and one of the most rapidly induced genes upon type I interferon stimulation...
  44. Dong C, Gao N, Ross B, Yu F. ISG15 in Host Defense Against Candida albicans Infection in a Mouse Model of Fungal Keratitis. Invest Ophthalmol Vis Sci. 2017;58:2948-2958 pubmed publisher
    b>ISG15, a di-ubiquitin-like protein, is critical for controlling certain viral and bacterial infections. We sought to determine if ISG15 plays a role in corneal innate immunity against Candida albicans (C...
  45. Okumura F, Lenschow D, Zhang D. Nitrosylation of ISG15 prevents the disulfide bond-mediated dimerization of ISG15 and contributes to effective ISGylation. J Biol Chem. 2008;283:24484-8 pubmed publisher
    The expression of the ubiquitin-like molecule ISG15 (UCRP) and protein modification by ISG15 (ISGylation) are strongly activated by interferon, genotoxic stress, and pathogen infection, suggesting that ISG15 plays an important role in ..
  46. Swaim C, Scott A, Canadeo L, Huibregtse J. Extracellular ISG15 Signals Cytokine Secretion through the LFA-1 Integrin Receptor. Mol Cell. 2017;68:581-590.e5 pubmed publisher
    b>ISG15 is a ubiquitin-like protein that functions in innate immunity both as an intracellular protein modifier and as an extracellular signaling molecule that stimulates IFN-γ secretion...
  47. Okabe Y, Kawane K, Nagata S. IFN regulatory factor (IRF) 3/7-dependent and -independent gene induction by mammalian DNA that escapes degradation. Eur J Immunol. 2008;38:3150-8 pubmed publisher
    ..These results indicate that the mammalian chromosomal DNA that accumulates in macrophages due to inefficient degradation activates genes in both IRF3/IRF7-dependent and -independent manners. ..
  48. Oudshoorn D, van Boheemen S, Sánchez Aparicio M, Rajsbaum R, Garcia Sastre A, Versteeg G. HERC6 is the main E3 ligase for global ISG15 conjugation in mouse cells. PLoS ONE. 2012;7:e29870 pubmed publisher
    ..Type I interferon (IFN) stimulates expression and conjugation of the ubiquitin-like modifier IFN-stimulated gene 15 (ISG15), thereby restricting replication of a wide variety of viruses...
  49. Ma X, Bartczak A, Zhang J, He W, Shalev I, Smil D, et al. Protein interferon-stimulated gene 15 conjugation delays but does not overcome coronavirus proliferation in a model of fulminant hepatitis. J Virol. 2014;88:6195-204 pubmed publisher
    ..protease-2 (PLP2), that removes both ubiquitin and the ubiquitin-like interferon (IFN)-stimulated gene 15 (ISG15) protein from target proteins...
  50. Real C, Megger D, Sitek B, Jahn Hofmann K, Ickenstein L, John M, et al. Identification of proteins that mediate the pro-viral functions of the interferon stimulated gene 15 in hepatitis C virus replication. Antiviral Res. 2013;100:654-61 pubmed
    In previous studies we identified the interferon stimulated gene 15 (ISG15) as a pro-viral host factor in the pathogenesis of hepatitis C virus (HCV) infection...
  51. Sainz B, Martín B, Tatari M, Heeschen C, Guerra S. ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells. Cancer Res. 2014;74:7309-20 pubmed publisher
    ..Here, we show that TAMs secrete the IFN-stimulated factor ISG15, which enhances CSC phenotypes in PDAC in vitro and in vivo...
  52. Albers J, Schulze J, Beil F, Gebauer M, Baranowsky A, Keller J, et al. Control of bone formation by the serpentine receptor Frizzled-9. J Cell Biol. 2011;192:1057-72 pubmed publisher
    ..We also identified the ubiquitin-like modifier Isg15 as one potential downstream mediator of Fzd9 in these cells...
  53. Nakka V, Lang B, Lenschow D, Zhang D, Dempsey R, Vemuganti R. Increased cerebral protein ISGylation after focal ischemia is neuroprotective. J Cereb Blood Flow Metab. 2011;31:2375-84 pubmed publisher
    Addition of a small peptide called ISG15 is known as ISGylation, which is an ubiquitin (ub)-like posttranslational modification...
  54. Huang Y, Wee S, Gunaratne J, Lane D, Bulavin D. Isg15 controls p53 stability and functions. Cell Cycle. 2014;13:2200-10 pubmed publisher
    ..In addition to polyubiquitination, we found that p53 is targeted for degradation through ISGylation. Isg15, a ubiquitin-like protein, covalently modifies p53 at 2 sites in the N and C terminus, and ISGylated p53 can be ..
  55. Yoshida H, Okabe Y, Kawane K, Fukuyama H, Nagata S. Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA. Nat Immunol. 2005;6:49-56 pubmed
  56. Franzi S, Salajegheh M, Nazareno R, Greenberg S. Type 1 interferons inhibit myotube formation independently of upregulation of interferon-stimulated gene 15. PLoS ONE. 2013;8:e65362 pubmed publisher
    ..Of these, IFN-stimulated gene 15 (ISG15) is one of the most upregulated, suggesting its possible involvement in the pathogenesis of this disease...
  57. Gall A, Treuting P, Elkon K, Loo Y, Gale M, Barber G, et al. Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. Immunity. 2012;36:120-31 pubmed publisher
    ..These findings reveal a stepwise progression of autoimmune disease in Trex1-deficient mice, with implications for the treatment of AGS and related disorders...
  58. Eduardo Correia B, Martínez Romero C, Garcia Sastre A, Guerra S. ISG15 is counteracted by vaccinia virus E3 protein and controls the proinflammatory response against viral infection. J Virol. 2014;88:2312-8 pubmed publisher
    Conjugation of ISG15 inhibits replication of several viruses...
  59. Yángüez E, García Culebras A, Frau A, Llompart C, Knobeloch K, Gutierrez Erlandsson S, et al. ISG15 regulates peritoneal macrophages functionality against viral infection. PLoS Pathog. 2013;9:e1003632 pubmed publisher
    ..The ubiquitin-like protein (UBL) ISG15 is a critical IFN-induced antiviral molecule that protects against several viral infections, but the mechanism by ..