PXD018299 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: Human, cancer, deISGylating enzyme, proteomics, USP18, ISG15, immunotherapy |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD018299
- Label: PRIDE project
- Name: Deep analysis of the USP18-dependent ISGylome and proteome unveils important roles for USP18 in tumour cell antigenicity and radiosensitivity