PXD023339

PXD023339 is an original dataset announced via ProteomeXchange.

Title	USP28 deletion and small molecule inhibition destabilises c-Myc and elicits regression of squamous cell lung carcinoma
Description	Lung 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.
HostingRepository	PRIDE
AnnounceDate	2024-07-30
AnnouncementXML	Submission_2024-07-30_03:29:03.037.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	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-03 23:58:21	ID requested
⏵ 1	2024-07-30 03:29:03	announced

10.7554/ELIFE.71596;

submitter keyword: ABPP, USP28,Lung squamous cell carcinoma (LSCC)

Benedikt Kessler
contact affiliation	Target Discovery Institute. Nuffield Department of Medicine. University of Oxford.
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/2024/07/PXD023339

PRIDE project URI

• PRIDE
  1. PXD023339
     1. Label: PRIDE project
     2. Name: USP28 deletion and small molecule inhibition destabilises c-Myc and elicits regression of squamous cell lung carcinoma