USP18 - a multifunctional component in the interferon response

Biosci Rep. 2018 Nov 15;38(6):BSR20180250. doi: 10.1042/BSR20180250. Print 2018 Dec 21.

Abstract

Ubiquitin-specific proteases (USPs) represent the largest family of deubiquitinating enzymes (DUB). These proteases cleave the isopeptide bond between ubiquitin and a lysine residue of a ubiquitin-modified protein. USP18 is a special member of the USP family as it only deconjugates the ubiquitin-like protein ISG15 (interferon-stimulated gene (ISG) 15) from target proteins but is not active towards ubiquitin. Independent of its protease activity, USP18 functions as a major negative regulator of the type I interferon response showing that USP18 is - at least - a bifunctional protein. In this review, we summarise our current knowledge of protease-dependent and -independent functions of USP18 and discuss the structural basis of its dual activity.

Keywords: ISG15; USP18; interferons; protease; ubiquitin like modifier proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cytokines / chemistry
  • Cytokines / genetics
  • Endopeptidases / chemistry*
  • Endopeptidases / genetics
  • Humans
  • Interferon Type I / chemistry*
  • Interferon Type I / genetics
  • Peptide Hydrolases / chemistry*
  • Peptide Hydrolases / genetics
  • Protein Conformation
  • Proteolysis
  • Signal Transduction / genetics
  • Ubiquitin / chemistry
  • Ubiquitin / genetics*
  • Ubiquitin Thiolesterase
  • Ubiquitins / chemistry
  • Ubiquitins / genetics

Substances

  • Cytokines
  • Interferon Type I
  • Ubiquitin
  • Ubiquitins
  • ISG15 protein, human
  • Endopeptidases
  • Peptide Hydrolases
  • USP18 protein, human
  • Ubiquitin Thiolesterase