PXD035450 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-07-20 04:53:36 | ID requested | |
⏵ 1 | 2023-04-04 15:43:07 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: kidney, FLCN, TFEB, TFE3, RCC |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035450
- Label: PRIDE project
- Name: TFEB AND TFE3 DRIVE KIDNEY CYSTOGENESIS AND TUMORIGENESIS