Imperial College London
Alternate

DrGraemeBirdsey

Faculty of Medicine, National Heart & Lung Institute

Senior Lecturer in Vascular Science
 
 
 
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Contact

 

+44 (0)20 7594 8633g.birdsey Website

 
 
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Location

 

535ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{D'Amico:2022:10.1242/dev.200528,
author = {D'Amico, G and Fernandez, I and Gómez-Escudero, J and Kim, H and Maniati, E and Azman, MS and Mardakheh, FK and Serrels, B and Serrels, A and Parsons, M and Squire, A and Birdsey, GM and Randi, AM and Bolado-Carrancio, A and Gangeswaran, R and Reynolds, LE and Bodrug, N and Wang, Y and Wang, J and Meier, P and Hodivala-Dilke, KM},
doi = {10.1242/dev.200528},
journal = {Development},
title = {ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning},
url = {http://dx.doi.org/10.1242/dev.200528},
volume = {149},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - D'Amico,G
AU  - Fernandez,I
AU  - Gómez-Escudero,J
AU  - Kim,H
AU  - Maniati,E
AU  - Azman,MS
AU  - Mardakheh,FK
AU  - Serrels,B
AU  - Serrels,A
AU  - Parsons,M
AU  - Squire,A
AU  - Birdsey,GM
AU  - Randi,AM
AU  - Bolado-Carrancio,A
AU  - Gangeswaran,R
AU  - Reynolds,LE
AU  - Bodrug,N
AU  - Wang,Y
AU  - Wang,J
AU  - Meier,P
AU  - Hodivala-Dilke,KM
DO  - 10.1242/dev.200528
PY  - 2022///
SN  - 0950-1991
TI  - ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning
T2  - Development
UR  - http://dx.doi.org/10.1242/dev.200528
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35723257
UR  - https://journals.biologists.com/dev/article/149/13/dev200528/275974/ERG-activity-is-regulated-by-endothelial-FAK
UR  - http://hdl.handle.net/10044/1/97853
VL  - 149
ER  -
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