PXD059919

PXD059919 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of a molecular glue to redirect lysine acetyltransferase for selective induction of cell death
Description	Lysine acetyltransferases (KATs) such as p300 and CBP regulate gene networks in healthy and malignant cells by scaffolding transcriptional machinery and by acetylating chromatin and transcription factors (TFs). In certain cancers including diffuse large B cell lymphomas, they contribute to tumor suppression and are therapeutic vulnerabilities when deregulated. Inhibitors and degraders of KATs are limited by potential toxicity associated with targeting these essential proteins. We introduce KAT-TCIPs (lysine acetyltransferase transcriptional/epigenetic chemical inducers of proximity), bivalent molecules that redirect the KAT and co-activating activity of p300 and CBP towards programmed cell death signaling repressed by the oncogenic TF BCL6. The lead KAT-TCIP molecule kills lymphoma cells at ~0.8 nM by redistributing chromatin acetylation, activating the pro-apoptotic protein PUMA, and repressing MYC. Analysis of the ternary co-crystal structure containing p300 and BCL6 reveals fortuitous interactions that drive the potency and specificity of KAT-TCIPs and sets a precedent for KAT-targeting induced proximity therapeutics.
HostingRepository	PRIDE
AnnounceDate	2026-07-22
AnnouncementXML	Submission_2026-07-22_13:26:31.192.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brendan Dwyer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-17 06:27:30	ID requested
⏵ 1	2026-07-22 13:26:31	announced

10.1016/J.CELL.2026.06.037;

submitter keyword: Human, cancer, transcription, induced proximity, molecular glues

Nathanael Gray
contact affiliation	Professor of Chemical and Systems Biology at Stanford, USA
contact email	nsgray01@stanford.edu
lab head
Brendan Dwyer
contact affiliation	Stanford University
contact email	dwyermrbrendan@gmail.com
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/2026/07/PXD059919

PRIDE project URI

• PRIDE
  1. PXD059919
     1. Label: PRIDE project
     2. Name: Proteomic analysis of a molecular glue to redirect lysine acetyltransferase for selective induction of cell death