PXD051575

PXD051575 is an original dataset announced via ProteomeXchange.

Title	A co-opted ISG15-USP18 binding mechanism normally reserved for deISGylation controls type I IFN signalling
Description	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 ISG15, evidenced by autoinflammatory disease in patients with inherited ISG15 deficiencies. Current models suggest that ISG15 stabilises 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-dependent stabilisation of USP18 involves transient hydrophobic interactions. Nonetheless, while USP18 stabilisation is necessary, it is not sufficient for regulation of IFN signalling. USP18 requires non-covalent interactions with the ISG15 C-terminal diGlycine motif to promote its regulatory function. This trait may have been acquired in humans through co-option of a binding mechanism normally reserved for deISGylation, identifying an unexpected new function for human ISG15.
HostingRepository	PRIDE
AnnounceDate	2025-03-07
AnnouncementXML	Submission_2025-03-07_02:22:57.919.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Weekes
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-19 04:59:05	ID requested
⏵ 1	2025-03-07 02:22:58	announced

10.1002/eji.202451651;

Vasou A, Nightingale K, Cetkovsk, á V, Scheler J, Bamford CGG, Andrejeva J, Rowe JC, Swatek KN, Schwarz-Linek U, Randall RE, McLauchlan J, Weekes MP, Bogunovic D, Hughes DJ, ISG15-Dependent Stabilisation of USP18 Is Necessary but Not Sufficient to Regulate Type I Interferon Signalling in Humans. Eur J Immunol, 55(2):e202451651(2025) [pubmed]

submitter keyword: ISGylation, ISG15, signalling,Interferon

Michael Weekes
contact affiliation	Cambridge Institute for Medical Research, University of Cambridge
contact email	mpw1001@cam.ac.uk
lab head
Michael Weekes
contact affiliation	University of Cambridge
contact email	mpw1001@cam.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/03/PXD051575

PRIDE project URI

• PRIDE
  1. PXD051575
     1. Label: PRIDE project
     2. Name: A co-opted ISG15-USP18 binding mechanism normally reserved for deISGylation controls type I IFN signalling