PXD066867

PXD066867 is an original dataset announced via ProteomeXchange.

Title	3x-HA Tagged PAF1 IP-Ms in MOLM-13 CAS9 cells
Description	Transcriptional regulatory proteins are frequent drivers of oncogenesis and common targets for drug discovery. The transcriptional co-activator, ENL, which binds to chromatin through an acetyllysine reader YEATS domain, is preferentially required for the survival and pathogenesis of acute leukemia. Small molecules that inhibit the ENL YEATS domain show anti-leukemia effects in preclinical models, which is thought to be caused by the downregulation of pro-leukemic ENL target genes. However, the transcriptional effects of ENL YEATS domain inhibitors have not been studied in models of intrinsic or acquired resistance and, therefore, the connection between proximal transcriptional effects and downstream anti-proliferative effects is poorly understood. To address this, we identified models of intrinsic and acquired resistance and used them to study the effects of ENL YEATS domain inhibitors. We first discovered that ENL YEATS domain inhibition produces similar transcriptional responses in naive models of sensitive and resistant leukemia. We then performed a CRISPR/Cas9-based genetic modifier screen and identified in-frame deletions of the essential transcriptional regulator, PAF1, that confer resistance to ENL YEATS domain inhibitors. Using isogenic models of PAF1-mediated resistance, we again found that the downregulation of ENL target genes is shared in both sensitive and resistant leukemia. Altogether, these data support the conclusion that the suppression of ENL target genes is not sufficient to explain the anti-leukemia effects of ENL antagonists.
HostingRepository	PRIDE
AnnounceDate	2025-10-21
AnnouncementXML	Submission_2025-10-21_09:24:55.319.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paige Barta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-01 10:59:44	ID requested
⏵ 1	2025-10-21 09:24:56	announced

Barta PA, Garnar-Wortzel L, Bishop TR, Hayward RE, Hargis LM, Shaum JB, Kwok HS, Liau BB, Cravatt BF, Erb MA, A chemical-genetic interaction between PAF1 and ENL/AF9 YEATS inhibition. bioRxiv, ():(2025) [pubmed]

10.1101/2025.09.09.675200;

submitter keyword: Human, Acute meyloid leukemia, Transcriptional regulation

Michael Erb
contact affiliation	Chemistry Department, The Scripps Research Institute, La Jolla, California, USA
contact email	michaelerb@scripps.edu
lab head
Paige Barta
contact affiliation	The Scripps Research Institute
contact email	pbarta@scripps.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/2025/10/PXD066867

PRIDE project URI

• PRIDE
  1. PXD066867
     1. Label: PRIDE project
     2. Name: 3x-HA Tagged PAF1 IP-Ms in MOLM-13 CAS9 cells