ISG15-Dependent Stabilisation of USP18 Is Necessary but Not Sufficient to Regulate Type I Interferon Signalling in Humans.

ABSTRACT: Type I interferon (IFN) signalling induces the expression of several hundred IFN-stimulated genes (ISGs) that provide an unfavourable environment for viral replication. To prevent an overexuberant response and autoinflammatory disease, IFN signalling requires tight control. One critical regulator is the ubiquitin-like protein IFN-stimulated gene 15 (ISG15), evidenced by autoinflammatory disease in patients with inherited ISG15 deficiencies. Current models suggest that ISG15 stabilises ubiquitin-specific peptidase 18 (USP18), a well-established negative regulator of IFN signalling. USP18 also functions as an ISG15-specific peptidase that cleaves ISG15 from ISGylated proteins; however, USP18's catalytic activity is dispensable for controlling IFN signalling. Here, we show that the ISG15-depe

SUBMITTER: Vasou A 

PROVIDER: S-EPMC11811815 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature