PXD033447

PXD033447 is an original dataset announced via ProteomeXchange.

Title	ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning
Description	Precise vascular patterning is critical for normal growth and development. The ERG transcription factor drives Delta like ligand 4 (DLL4)/Notch signalling and is thought to act as pivotal regulators of endothelial cell (EC) dynamics and developmental angiogenesis. However, molecular regulation of ERG activity remains obscure. Using a series of EC specific Focal Adhesion Kinase (FAK)-knockout (KO) and point-mutant FAK-knockin mice, we show that loss of ECFAK, its kinase activity or phosphorylation at FAK-Y397, but not FAK-Y861, reduces ERG and DLL4 expression levels together with concomitant aberrations in vascular patterning. Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins identified that endothelial nuclear-FAK interacts with the de-ubiquitinase USP9x and the ubiquitin ligase TRIM25 enzymes. Further in silico analysis corroborates that ERG interacts with USP9x and TRIM25. Moreover, ERG levels are reduced in FAKKO ECs via a ubiquitin-mediated post-translational modification programme involving USP9x and TRIM25. Re-expression of ERG in vivo and in vitro rescues the aberrant vessel sprouting defects observed in the absence of ECFAK. Our findings identify ECFAK as a regulator of retinal vascular patterning by controlling ERG protein degradation via TRIM25/USP9x.
HostingRepository	PRIDE
AnnounceDate	2022-07-05
AnnouncementXML	Submission_2022-07-05_03:21:17.211.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex von kriegsheim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-25 04:09:16	ID requested
⏵ 1	2022-07-05 03:21:18	announced

D'Amico G, Fernandez I, G, ó, mez-Escudero J, Kim H, Maniati E, Azman MS, Mardakheh FK, Serrels B, Serrels A, Parsons M, Squire A, Birdsey GM, Randi AM, Bolado-Carrancio A, Gangeswaran R, Reynolds LE, Bodrug N, Wang Y, Wang J, Meier P, Hodivala-Dilke KM, ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning. Development, 149(13):(2022) [pubmed]

submitter keyword: RIME, HUVEC, FAK

Alex von Kriegsheim
contact affiliation	University of Edinburgh
contact email	avonkri@ed.ac.uk
lab head
Alex von kriegsheim
contact affiliation	University of Edinburgh
contact email	alex.vonkriegsheim@ucd.ie
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033447
     1. Label: PRIDE project
     2. Name: ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning