PXD035450-1

PXD035450 is an original dataset announced via ProteomeXchange.

Title	TFEB AND TFE3 DRIVE KIDNEY CYSTOGENESIS AND TUMORIGENESIS
Description	Birt-Hogg-Dubè (BHD) syndrome is an inherited condition caused by loss-of-function mutations in the gene encoding the tumor-suppressor protein folliculin (FLCN) and frequently associated with kidney cysts and cancer. FLCN acts as a negative regulator of TFEB and TFE3 transcription factors, master controllers of lysosomal biogenesis and autophagy, by enabling their phosphorylation by the mechanistic Target Of Rapamycin Complex 1 (mTORC1). We previously showed that deletion of TFEB rescued the renal cystic phenotype of kidney-specific Flcn KO mice. Using Flcn/TFEB/TFE3 double and triple KO mice we now show that both TFEB and TFE3 contribute, in a differential and cooperative manner, to kidney cystogenesis. Importantly, silencing of either TFEB or TFE3 rescued tumorigenesis in patient-derived xenografts (PDXs) generated from a kidney tumor of a BHD patient. Furthermore, transcriptome analyses performed in transgenic mice, PDXs and patient tumor samples revealed TFEB/TFE3 downstream targets that may contribute to their tumorigenic activity. Our findings demonstrate in disease-relevant models that TFEB and TFE3 are key drivers of kidney tumorigenesis and suggest novel therapeutic strategies based on the inhibition of these transcription factors.
HostingRepository	PRIDE
AnnounceDate	2023-04-04
AnnouncementXML	Submission_2023-04-04_15:43:07.362.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chiara Di Malta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-20 04:53:36	ID requested
⏵ 1	2023-04-04 15:43:07	announced

Dataset with its publication pending

submitter keyword: kidney, FLCN, TFEB, TFE3, RCC

Chiara DiMalta
contact affiliation	Telethon Institute of Genetics and Medicine (TIGEM) Department of Translational Medicine, University of Naples "Federico II", Italy
contact email	dimalta@tigem.it
lab head
Chiara Di Malta
contact affiliation	Telethon Institute of Genetics and Medicine
contact email	dimalta@tigem.it
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/2023/04/PXD035450

PRIDE project URI

• PRIDE
  1. PXD035450
     1. Label: PRIDE project
     2. Name: TFEB AND TFE3 DRIVE KIDNEY CYSTOGENESIS AND TUMORIGENESIS