ISG15 antiviral mechanism

Stable Identifier
Homo sapiens
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Interferon-stimulated gene 15 (ISG15) is a member of the ubiquitin-like (Ubl) family. It is strongly induced upon exposure to type I Interferons (IFNs), viruses, bacterial LPS, and other stresses. Once released the mature ISG15 conjugates with an array of target proteins, a process termed ISGylation. ISGylation utilizes a mechanism similar to ubiquitination, requiring a three-step enzymatic cascade. UBE1L is the ISG15 E1 activating enzyme which specifically activates ISG15 at the expense of ATP. ISG15 is then transfered from E1 to the E2 conjugating enzyme UBCH8 and then to the target protein with the aid of an ISG15 E3 ligase, such as HERC5 and EFP. Hundreds of target proteins for ISGylation have been identified. Several proteins that are part of antiviral signaling pathways, such as RIG-I, MDA5, Mx1, PKR, filamin B, STAT1, IRF3 and JAK1, have been identified as targets for ISGylation. ISG15 also conjugates some viral proteins, inhibiting viral budding and release. ISGylation appears to act either by disrupting the activity of a target protein and/or by altering its localization within the cell.

Literature References
PubMed ID Title Journal Year
20946978 Emerging role of ISG15 in antiviral immunity

Chen, ZJ, Skaug, B

Cell 2010
16009940 Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways

Denison, C, Krug, RM, Huibregtse, JM, Gygi, S, Zhao, C

Proc Natl Acad Sci U S A 2005
  Antiviral Properties of ISG15

Lenschow, DJ

20153823 ISG15 and immune diseases

Jeon, YJ, Yoo, HM, Chung, CH

Biochim Biophys Acta 2010
15970528 ISG15: a ubiquitin-like enigma

Zhang, DE, Dao, CT

Front Biosci 2005
12582176 High-throughput immunoblotting. Ubiquitiin-like protein ISG15 modifies key regulators of signal transduction

Malakhova, OA, Malakhov, MP, Zhang, DE, Jacobs, BS, Borden, EC, Kim, KI

J Biol Chem 2003
Orthologous Events
Cross References
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