PXD066112

PXD066112 is an original dataset announced via ProteomeXchange.

Title	KLF5 co-immunoprecipitation mass spectrometry
Description	Lineage plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and contributes to tumor heterogeneity and therapeutic resistance. Here, we identify KLF5 as a dynamic master regulator of epithelial lineage identity in PDAC, with dichotomous roles in promoting either classical or basal-like transcriptional programs. Through unbiased proteomic and genetic screens, we uncover the AAA+ ATPases RUVBL1 and RUVBL2 as essential coactivators of KLF5 across both lineage states. We demonstrate that ATP hydrolysis by RUVBL1/2 is required for the stable interaction with an intrinsically disordered region of KLF5, enabling its recruitment to lineage-specific enhancers and driving transcriptional regulation of identity-defining genes. Notably, small-molecule inhibitors of RUVBL1/2 ATPase activity, which have anti-PDAC activity in vivo, suppress KLF5-dependent transcription. These findings define a previously unrecognized mechanism of ATP hydrolysis-dependent transcriptional coactivation by AAA+ ATPases and highlight a potential therapeutic strategy for modulating aberrant lineage programs in cancer. This project contains files relative to a Co-IP MS with KLF5-MBP as bait.
HostingRepository	PRIDE
AnnounceDate	2025-08-21
AnnouncementXML	Submission_2025-08-21_04:49:06.597.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paolo Cifani
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-14 14:12:32	ID requested
⏵ 1	2025-08-21 04:49:06	announced

Dataset with its publication pending

submitter keyword: KLF5 Co-IP PDAC

Paolo Cifani
contact affiliation	Cold Spring Harbor Laboratory
contact email	cshl.mass.spec@gmail.com
lab head
Paolo Cifani
contact affiliation	Cold Spring Harbor Laboratory
contact email	cshl.mass.spec@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066112
     1. Label: PRIDE project
     2. Name: KLF5 co-immunoprecipitation mass spectrometry