PXD055843

PXD055843 is an original dataset announced via ProteomeXchange.

Title	USP24 is an ISG15 cross-reactive deubiquitinase that mediates IFN-I production by de-ISGylating the RNA helicase MOV10
Description	The interferon Stimulated Gene-15 (ISG15) is a ubiquitin-like modifier induced by type I Interferon (IFN-I) and plays a crucial role in the innate immune response against viral infections. ISG15 is conjugated to target proteins by an enzymatic cascade through a process called ISGylation. While USP18 is a well-defined deISGylase counteracting ISG15 conjugation, ISG15 cross-reactive deubiquitylating enzymes (DUBs) have also been reported. Our study reports USP24 as a novel ISG15 cross-reactive DUB identified through activity-based protein profiling (ABPP). We demonstrated that recombinant USP24 processed pro-ISG15 and ISG15-linked synthetic substrates in vitro. Moreover, the depletion of USP24 significantly increased the accumulation of ISG15 conjugates upon IFN-β stimulation. An extensive proteomic analysis of the USP24-dependent ISGylome, integrating total proteome, GG-peptidome, and ISG15 interactome data, identified MOV10 as a specific target of USP24 for deISGylation. Further validation in cells revealed that ISGylated MOV10 enhances IFN-β production, whereas USP24 deISGylates MOV10 to negatively regulate the innate immune response. This study showcase USP24's novel roles in modulating ISGylation, IFN-I production, and innate immune responses with therapeutic implications in infectious diseases, cancer, autoimmunity, and neuroinflammation.
HostingRepository	PRIDE
AnnounceDate	2026-05-14
AnnouncementXML	Submission_2026-05-13_17:27:16.280.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Adan Pinto-Fernandez
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-13 03:41:43	ID requested
⏵ 1	2026-05-13 17:27:16	announced

Dataset with its publication pending

submitter keyword: Human, Innate Immunity, Ubiquitomics, ISG15, Immunology, USP24

Adan Pinto-Fernandez
contact affiliation	COI-NDM (University of Oxford)
contact email	adan.pintofernandez@ndm.ox.ac.uk
lab head
Adan Pinto-Fernandez
contact affiliation	University of Oxford
contact email	adan.pintofernandez@ndm.ox.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/2026/05/PXD055843

PRIDE project URI

• PRIDE
  1. PXD055843
     1. Label: PRIDE project
     2. Name: USP24 is an ISG15 cross-reactive deubiquitinase that mediates IFN-I production by de-ISGylating the RNA helicase MOV10