PXD065292-1

PXD065292 is an original dataset announced via ProteomeXchange.

Title	Targeting histone H2B acetylated enhanceosomes via p300/CBP degradation in prostate cancer
Description	Prostate cancer is driven by oncogenic transcription factor enhanceosomes comprising chromatin and epigenetic regulators. The lysine acetyltransferases p300 and CBP are key cofactors that activate enhancers through histone acetylation. Here, we identify p300/CBP-mediated multisite acetylation of the histone H2B N-terminus (H2BNTac) as a defining feature of oncogenic enhanceosomes in androgen receptor (AR)-positive prostate cancer. p300/CBP are essential for AR and ERG transcriptional activity, and their dual degradation eliminates H2BNTac and H3K27ac marks at hyperactive enhancers more effectively than targeting either paralog or bromodomains alone. Cytotoxicity profiling across >900 cell lines revealed that tumors with high H2BNTac, including AR-positive prostate cancer, are selectively dependent on p300/CBP. In preclinical models, systemic p300/CBP degradation inhibited tumor growth, synergized with AR antagonists, and showed no evident toxicity. These findings position H2BNTac as a key epigenetic marker of enhancer addiction and support dual p300/CBP degradation as a promising therapy for enhancer-driven cancers.
HostingRepository	PRIDE
AnnounceDate	2025-07-28
AnnouncementXML	Submission_2025-07-28_14:34:58.941.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jie Luo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-22 09:26:23	ID requested
⏵ 1	2025-07-28 14:34:59	announced

Dataset with its publication pending

submitter keyword: acetyl-lysine proteomics,prostate cancer, p300/CBP, PROTAC degrader

Arul Chinnaiyan
contact affiliation	MCTP,Rogel cancer center, Ann Arbor, Michigan, 48109
contact email	luojie@med.umich.edu
lab head
Jie Luo
contact affiliation	University of Michigan
contact email	luojie@med.umich.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/2025/07/PXD065292

PRIDE project URI

• PRIDE
  1. PXD065292
     1. Label: PRIDE project
     2. Name: Targeting histone H2B acetylated enhanceosomes via p300/CBP degradation in prostate cancer