ISG15

ISG15 ubiquitin-like modifier, also known as ISG15, is a human gene. [cite web | title = Entrez Gene: ISG15 ISG15 ubiquitin-like modifier| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9636| accessdate = ] ISG15 shares several common properties with other ubiquitin-like molecules (UBLs), but its activity is tightly regulated by specific signaling pathways that have a role in innate immunity. ISG15 was identified as an interferon stimulated gene (ISG) since its expression is induced in response to type I interferons or lipopolysaccharide treatment. Upon interferon treatment, ISG15 can be detected in both free and conjugated forms, and is secreted from monocytes and lymphocytes where it can function as a cytokine. In the cell, ISG15 co-localizes with intermediate filaments and ISGylation may modulate the JAK-STAT pathway or certain aspects of neurological disease. It is also known as UCRP (ubiquitin cross-reactive protein) since it contains 2 tandem ubiquitin homology domains and is cross-reactive with ubiquitin antibodies. In contrast to other UBLs, ISG15 has not been identified in lower eukaryotes (yeast, nematode, insects, plants) indicating its role in specialized functions.

The mechanism of ISGylation and deISGylation is similar to that of ubiquitin, although the complete system components have not yet been identified. The activating E1 enzyme (UBE1L) charges ISG15 by forming a high-energy thiolester intermediate and transfers it to the UbcH8 E2 protein. UbcH8 has been identified as the major E2 for ISGlyation, although it also functions in ubiquitination. The E2 protein subsequently transfers the ISG15 to specific E3 ligases (none have been identified to date) and relevant intracellular substrates. Only one deconjugating protease with specificity to ISG15 has been identified to date: UBP43 (a member of the USP family) cleaves ISG15-peptide fusions and also removes ISG15 (deISGylation) from native conjugates. [cite web | title = Boston Biochem ISG15 Overview| url = http://www.bostonbiochem.com/overview.php?prod=isg15| accessdate = 2008-05-21]

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References

Further reading

*cite journal | author=Bektas N, Noetzel E, Veeck J, "et al." |title=The ubiquitin-like molecule interferon-stimulated gene 15 as a potential prognostic marker in human breast cancer |journal=Breast Cancer Res. |volume=10 |pages= R58 |year= 2008 |pmid= 18627608 |doi= 10.1186/bcr2117 PBB_Further_reading
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*cite journal | author=Andersen JB, Hassel BA |title=The interferon regulated ubiquitin-like protein, ISG15, in tumorigenesis: friend or foe? |journal=Cytokine Growth Factor Rev. |volume=17 |issue= 6 |pages= 411–21 |year= 2007 |pmid= 17097911 |doi= 10.1016/j.cytogfr.2006.10.001
*cite journal | author=Loeb KR, Haas AL |title=The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins. |journal=J. Biol. Chem. |volume=267 |issue= 11 |pages= 7806–13 |year= 1992 |pmid= 1373138 |doi=
*cite journal | author=Clauss IM, Wathelet MG, Szpirer J, "et al." |title=Chromosomal localization of two human genes inducible by interferons, double-stranded RNA, and viruses. |journal=Cytogenet. Cell Genet. |volume=53 |issue= 2-3 |pages= 166–8 |year= 1990 |pmid= 1695131 |doi=
*cite journal | author=Knight E, Cordova B |title=IFN-induced 15-kDa protein is released from human lymphocytes and monocytes. |journal=J. Immunol. |volume=146 |issue= 7 |pages= 2280–4 |year= 1991 |pmid= 2005397 |doi=
*cite journal | author=Haas AL, Ahrens P, Bright PM, Ankel H |title=Interferon induces a 15-kilodalton protein exhibiting marked homology to ubiquitin. |journal=J. Biol. Chem. |volume=262 |issue= 23 |pages= 11315–23 |year= 1987 |pmid= 2440890 |doi=
*cite journal | author=Feltham N, Hillman M, Cordova B, "et al." |title=A 15-kD interferon-induced protein and its 17-kD precursor: expression in Escherichia coli, purification, and characterization. |journal=J. Interferon Res. |volume=9 |issue= 5 |pages= 493–507 |year= 1989 |pmid= 2477469 |doi=
*cite journal | author=Blomstrom DC, Fahey D, Kutny R, "et al." |title=Molecular characterization of the interferon-induced 15-kDa protein. Molecular cloning and nucleotide and amino acid sequence. |journal=J. Biol. Chem. |volume=261 |issue= 19 |pages= 8811–6 |year= 1986 |pmid= 3087979 |doi=
*cite journal | author=Knight E, Fahey D, Cordova B, "et al." |title=A 15-kDa interferon-induced protein is derived by COOH-terminal processing of a 17-kDa precursor. |journal=J. Biol. Chem. |volume=263 |issue= 10 |pages= 4520–2 |year= 1988 |pmid= 3350799 |doi=
*cite journal | author=Reich N, Evans B, Levy D, "et al." |title=Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 18 |pages= 6394–8 |year= 1987 |pmid= 3476954 |doi=
*cite journal | author=Lowe J, McDermott H, Loeb K, "et al." |title=Immunohistochemical localization of ubiquitin cross-reactive protein in human tissues. |journal=J. Pathol. |volume=177 |issue= 2 |pages= 163–9 |year= 1996 |pmid= 7490683 |doi= 10.1002/path.1711770210
*cite journal | author=Loeb KR, Haas AL |title=Conjugates of ubiquitin cross-reactive protein distribute in a cytoskeletal pattern. |journal=Mol. Cell. Biol. |volume=14 |issue= 12 |pages= 8408–19 |year= 1994 |pmid= 7526157 |doi=
*cite journal | author=Narasimhan J, Potter JL, Haas AL |title=Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from that of ubiquitin. |journal=J. Biol. Chem. |volume=271 |issue= 1 |pages= 324–30 |year= 1996 |pmid= 8550581 |doi=
*cite journal | author=D'Cunha J, Ramanujam S, Wagner RJ, "et al." |title=In vitro and in vivo secretion of human ISG15, an IFN-induced immunomodulatory cytokine. |journal=J. Immunol. |volume=157 |issue= 9 |pages= 4100–8 |year= 1996 |pmid= 8892645 |doi=
*cite journal | author=Smith JK, Siddiqui AA, Krishnaswamy GA, "et al." |title=Oral use of interferon-alpha stimulates ISG-15 transcription and production by human buccal epithelial cells. |journal=J. Interferon Cytokine Res. |volume=19 |issue= 8 |pages= 923–8 |year= 1999 |pmid= 10476939 |doi= 10.1089/107999099313460
*cite journal | author=Bebington C, Doherty FJ, Fleming SD |title=Ubiquitin cross-reactive protein gene expression is increased in decidualized endometrial stromal cells at the initiation of pregnancy. |journal=Mol. Hum. Reprod. |volume=5 |issue= 10 |pages= 966–72 |year= 1999 |pmid= 10508226 |doi=
*cite journal | author=Nyman TA, Matikainen S, Sareneva T, "et al." |title=Proteome analysis reveals ubiquitin-conjugating enzymes to be a new family of interferon-alpha-regulated genes. |journal=Eur. J. Biochem. |volume=267 |issue= 13 |pages= 4011–9 |year= 2000 |pmid= 10866800 |doi=
*cite journal | author=Yuan W, Krug RM |title=Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. |journal=EMBO J. |volume=20 |issue= 3 |pages= 362–71 |year= 2001 |pmid= 11157743 |doi= 10.1093/emboj/20.3.362
*cite journal | author=Malakhov MP, Malakhova OA, Kim KI, "et al." |title=UBP43 (USP18) specifically removes ISG15 from conjugated proteins. |journal=J. Biol. Chem. |volume=277 |issue= 12 |pages= 9976–81 |year= 2002 |pmid= 11788588 |doi= 10.1074/jbc.M109078200
*cite journal | author=Meraro D, Gleit-Kielmanowicz M, Hauser H, Levi BZ |title=IFN-stimulated gene 15 is synergistically activated through interactions between the myelocyte/lymphocyte-specific transcription factors, PU.1, IFN regulatory factor-8/IFN consensus sequence binding protein, and IFN regulatory factor-4: characterization of a new subtype of IFN-stimulated response element. |journal=J. Immunol. |volume=168 |issue= 12 |pages= 6224–31 |year= 2002 |pmid= 12055236 |doi=
*cite journal | author=Padovan E, Terracciano L, Certa U, "et al." |title=Interferon stimulated gene 15 constitutively produced by melanoma cells induces e-cadherin expression on human dendritic cells. |journal=Cancer Res. |volume=62 |issue= 12 |pages= 3453–8 |year= 2002 |pmid= 12067988 |doi=

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