PXD018559-2

PXD018559 is an original dataset announced via ProteomeXchange.

Title	A comprehensive enhancer screen identifies TRAM2 as a key mediator of YAP oncogenesis
Description	Frequent activation of the co-transcriptional factor YAP is observed in a large number of solid tumors. Activated-YAP associates with enhancer loci via TEAD4-DNA-binding protein, and stimulates cancer aggressiveness. Although thousands of YAP/TEAD4 binding-sites were annotated, their functional importance is unknow. Here, we implemented a genetic approach to uncover functions of YAP/TEAD4-associated enhancers, demonstrated its robustness, and used it to reveal a network of enhancers required for YAP-mediated proliferation. We focused on Enhancer TRAM2, as its target gene TRAM2 showed the strongest expression-correlation with YAP in nearly all tumor types. Interestingly, TRAM2 phenocopied YAP-induced cell proliferation, migration and invasion phenotypes, and correlated with poor patient survival. Mechanistically, we identified FSTL-1 as a major direct client of TRAM2 that is involved in these phenotypes. Thus, TRAM2 is a key novel mediator of YAP-induced oncogenic proliferation and cellular invasiveness.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:17:52.087.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Onno Bleijerveld
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF-X; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-14 23:54:14	ID requested
1	2021-01-14 05:55:03	announced
⏵ 2	2024-10-22 05:17:52	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: enhancer, breast cancer,YAP, TRAM2, gene regulation, migration, invasion, proliferation, proteome, LC-MS/MS

Maarten Altelaar
contact affiliation	Head of NKI Proteomics Facility
contact email	m.altelaar@nki.nl
lab head
Onno Bleijerveld
contact affiliation	The Netherlands Cancer Institute
contact email	o.bleijerveld@nki.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018559
     1. Label: PRIDE project
     2. Name: A comprehensive enhancer screen identifies TRAM2 as a key mediator of YAP oncogenesis