PXD066297-1

PXD066297 is an original dataset announced via ProteomeXchange.

Title	Genome-scale CRISPR screens identify PTGES3 as a direct modulator of AR function in advanced prostate cancer
Description	The androgen receptor (AR) is a critical driver of prostate cancer (PCa). To study regulators of AR protein levels and oncogenic activity, we created the first live cell quantitative endogenous AR fluorescent reporters. Leveraging this novel AR reporter, we performed genome-scale CRISPRi flow cytometry sorting screens to systematically identify genes that modulate AR protein levels. We identified and validated known AR protein regulators including HOXB13 and GATA2 and also unexpected top hits including PTGES3, a poorly characterized gene in PCa. PTGES3 repression resulted in loss of AR protein, cell cycle arrest, and cell death in AR-driven PCa models. PTGES3 is not a commonly essential gene, and our data nominate it as a prime PCa drug target. Clinically, analysis of PCa data demonstrate that PTGES3 expression is associated with AR directed therapy resistance. Mechanistically, we show PTGES3 binds directly to AR, forms a protein complex with AR in the nucleus, regulates AR protein stability in vitro and in vivo and modulates AR function in the nucleus at AR target genes. Lastly using a disulfide tethering fragment screen, we developed a PTGES3 covalent inhibitor that blocks the PTGES3/AR interaction and represses AR signaling in PCa cells, suggesting PTGES3 inhibitors may be a next generation AR-targeting therapeutic strategy that can overcome known mechanisms of resistance to existing AR-directed therapies in PCa.
HostingRepository	PRIDE
AnnounceDate	2025-08-08
AnnouncementXML	Submission_2025-08-08_12:52:20.984.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Abhilash Barpanda
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-17 23:07:17	ID requested
⏵ 1	2025-08-08 12:52:21	announced

Dataset with its publication pending

submitter keyword: AR,CRISPR Screens, PTGES3, Prostate Cancer

Arun Wiita
contact affiliation	Department of Laboratory Medicine, UCSF
contact email	Arun.Wiita@ucsf.edu
lab head
Abhilash Barpanda
contact affiliation	IIT Bombay
contact email	avilash94@iitb.ac.in
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/2025/08/PXD066297

PRIDE project URI

• PRIDE
  1. PXD066297
     1. Label: PRIDE project
     2. Name: Genome-scale CRISPR screens identify PTGES3 as a direct modulator of AR function in advanced prostate cancer