PXD018299-2

PXD018299 is an original dataset announced via ProteomeXchange.

Title	Deep analysis of the USP18-dependent ISGylome and proteome unveils important roles for USP18 in tumour cell antigenicity and radiosensitivity
Description	The deubiquitylating enzyme USP18 is a major negative regulator of the interferon (IFN) signalling cascade. IFN pathways contribute to resistance to conventional chemotherapy, radiotherapy, and immunotherapy and are often upregulated in certain tumours, including breast, lung, and colon tumours. USP18 is the predominant human protease that cleaves interferon-stimulated gene ISG15, a ubiquitin-like protein tightly regulated in the context of innate immunity, from its modified substrate proteins in vivo. In this study, using advanced proteomic techniques, we have expanded the USP18-dependent ISGylome and proteome in a chronic myeloid leukaemia (CML)-derived cell line (HAP1) treated with type I IFN. Novel ISGylation targets were characterised that modulate the sensing of innate ligands, antigen presentation and secretion of cytokines. Consequently, CML USP18-deficient cells are more antigenic, driving increased activation of cytotoxic T lymphocytes (CTLs) and are more susceptible to irradiation. Our results suggest USP18 as a pharmacological target in cancer immunotherapy and radiotherapy.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:31:57.685.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: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine; monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion Lumos; Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-31 02:21:03	ID requested
1	2022-02-15 11:50:13	announced
⏵ 2	2024-10-22 05:31:58	announced	2024-10-22: Updated project metadata.

10.1038/s41416-020-01167-y;

Pinto-Fernandez A, Salio M, Partridge T, Chen J, Vere G, Greenwood H, Olie CS, Damianou A, Scott HC, Pegg HJ, Chiarenza A, D, í, az-Saez L, Smith P, Gonzalez-Lopez C, Patel B, Anderton E, Jones N, Hammonds TR, Huber K, Muschel R, Borrow P, Cerundolo V, Kessler BM, Deletion of the deISGylating enzyme USP18 enhances tumour cell antigenicity and radiosensitivity. Br J Cancer, 124(4):817-830(2021) [pubmed]

submitter keyword: Human, cancer, deISGylating enzyme, proteomics, USP18, ISG15, immunotherapy

Benedikt Kessler
contact affiliation	TDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK
contact email	benedikt.kessler@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/2022/02/PXD018299

PRIDE project URI

• PRIDE
  1. PXD018299
     1. Label: PRIDE project
     2. Name: Deep analysis of the USP18-dependent ISGylome and proteome unveils important roles for USP18 in tumour cell antigenicity and radiosensitivity