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To study the function of KLF5 in squamous cancers and gastrointestinal cancers [RNA-seq]

ABSTRACT: To study the function of KLF5 in squamous cancers and gastrointestinal cancers [RNA-seq]

PROVIDER: PRJNA622286 | ENA |

REPOSITORIES: ENA

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Dataset's files

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			Action	DRS
	SRR11459777_1.fastq.gz	Fastqsanger.gz
	SRR11459777_2.fastq.gz	Fastqsanger.gz
	SRR11459778_1.fastq.gz	Fastqsanger.gz
	SRR11459778_2.fastq.gz	Fastqsanger.gz
	SRR11459779_1.fastq.gz	Fastqsanger.gz

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KLF5 co-immunoprecipitation mass spectrometry

Project 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.

2025-08-21 | PXD066112 | Pride

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