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PXD023339

PXD023339 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleUSP28 deletion and small molecule inhibition destabilises c-Myc and elicits regression of squamous cell lung carcinoma
DescriptionLung squamous cell carcinoma (LSCC) is a considerable global health burden, with an incidence of over 600,000 cases per year. Treatment options are limited, and patient 5-year survival rate is less than 5%. The ubiquitin specific protease 28 (USP28) has been implicated in tumorigenesis through its stabilization of the oncoprotein c-MYC. Here, we show that genetic inactivation of USP28 induced regression of established murine LSCC lung tumors. We developed small molecule USP28 inhibitors that inhibit USP28 activity in the low nanomole range. While displaying considerable activity against the closest homologue USP25, these inhibitors showed a high degree of selectivity over other deubiquitinases. USP28 inhibitor treatment resulted in a dramatic decrease in c-Myc proteins levels and consequently induced substantial regression of autochthonous murine LSCC tumors and human LSCC xenografts, thereby phenocopying the effect observed by genetic deletion. Thus, USP28 may represent a promising therapeutic target for the treatment of squamous cell lung carcinoma.
HostingRepositoryPRIDE
AnnounceDate2024-07-30
AnnouncementXMLSubmission_2024-07-30_03:29:03.037.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAdan Pinto-Fernandez
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-01-03 23:58:21ID requested
12024-07-30 03:29:03announced
Publication List
10.7554/ELIFE.71596;
Keyword List
submitter keyword: ABPP, USP28,Lung squamous cell carcinoma (LSCC)
Contact List
Benedikt Kessler
contact affiliationTarget Discovery Institute. Nuffield Department of Medicine. University of Oxford.
contact emailbenedikt.kessler@ndm.ox.ac.uk
lab head
Adan Pinto-Fernandez
contact affiliationUniversity of Oxford
contact emailadan.pintofernandez@ndm.ox.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
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