PXD059902-1

PXD059902 is an original dataset announced via ProteomeXchange.

Title	Deep quantitative proteomics of TNBC and SUM149 cell lines treated with USP7 inhibitors
Description	The deubiquitinase USP7 plays an important role in tumorigenesis and is a key regulator of the MDM-p53 pathway. Emerging evidence also supports USP7’s p53-independent roles in proliferation and tumorigenesis. Triple negative breast cancers recurrently inactivate p53 and this disease subtype remains difficult to treat and in need of new therapeutic options. We show here that USP7 is upregulated at the protein level in TNBC patient tumors. Importantly, genetic and pharmacologic USP7 inactivation impaired tumor progression in TNBC animal models. To gain insight into the role of USP7 in p53-mutant TNBCs, we performed deep quantitative proteomics in multiple TNBC cell lines. This revealed an overlapping set of USP7 targets which collectively contribute to cell proliferation and survival. Acute USP7 inactivation allowed us to infer proximally controlled proteins which are likely direct targets. Surprisingly, many of the proteins downregulated by USP7 inhibition are E3 ubiquitin ligases. Thus, a key function of USP7 antagonizes the degradation of enzymes that perform ubiquitination, since these enzymes are often susceptible to auto-ubiquitination and degradation. We validate several new substrates, including the dual ubiquitin- and SUMO-ligase TOPORS, which is implicated in DNA damaging signaling. We find that TOPORS interacts with the BRCA1-A DNA damage repair complex suggesting a USP7-TOPORS-BRAC1-A axis that might further explain the continued proliferation of genomically unstable TNBCs. Collectively, these data nominate USP7 as a potential therapeutic in TNBC through its role in maintaining proteostasis.
HostingRepository	PRIDE
AnnounceDate	2026-05-21
AnnouncementXML	Submission_2026-05-21_12:39:51.615.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Angie Mordant
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-16 18:10:02	ID requested
⏵ 1	2026-05-21 12:39:52	announced

Dataset with its publication pending

submitter keyword: TNBC, Deubiquitinase, protein degradation,ubiquitin, USP7

Michael Emanuele
contact affiliation	Lineberger Comprehensive Cancer Center, UNC Chapel Hill
contact email	emanuele@email.unc.edu
lab head
Angie Mordant
contact affiliation	UNC Proteomics Core, Department of Pharmacology, University of North Carolina at Chapel Hill
contact email	angie_mordant@med.unc.edu
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/PXD059902

PRIDE project URI

• PRIDE
  1. PXD059902
     1. Label: PRIDE project
     2. Name: Deep quantitative proteomics of TNBC and SUM149 cell lines treated with USP7 inhibitors