Deubiquitinase USP10 regulates Notch signaling in the endothelium

Lim R
Max Planck Institute for Heart and Lung Research
January 1, 2019
Science
https://pubmed.ncbi.nlm.nih.gov/30975888

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/30975888

Research summary

In endothelial cells, USP10 interacts with and stabilizes the NOTCH1 intracellular domain (NICD1), slowing its ubiquitin-dependent turnover. Endothelial-specific deletion of Usp10 (via Pdgfb‑creERT2 in Usp10^fl/fl) increases vessel sprouting and tip-cell formation in postnatal mouse retina, phenocopying reduced Notch signaling; USP10 loss partially rescues ectopic NICD1 overexpression vascular defects repisalud.isciii.es+14pubmed.ncbi.nlm.nih.gov+14researchgate.net+14

Key outcome of the study

Endothelial deletion of Usp10 destabilizes NICD1, reduces canonical Notch target activation; increases EC density and filopodia in retinal angiogenesis; rescues NICD1‑overexpression vascular anomalies

Model

Pdgfb‑creERT2; Usp10^fl/fl endothelial-specific, inducible knockout (genOway-generated, C57BL/6)

TARGET:
Usp10
Synonyms:
Usp-10, Ubp3

Keywords

Vascular morphogenesis; angiogenic sprouting; endothelial Notch signaling; ocular vascular development; tip/stalk cell patterning

Technical specifications

Conditional floxed allele (exons 7‑8 flanked by loxP); inducible CreERT2 under Pdgfb promoter; tamoxifen dosing P1–P4; retinal angiogenesis assay at P7; germline KO lethal

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