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Deubiquitinase USP10 regulates Notch signaling in the endothelium

Item Type:Article
Title:Deubiquitinase USP10 regulates Notch signaling in the endothelium
Creators Name:Lim, R. and Sugino, T. and Nolte, H. and Andrade, J. and Zimmermann, B. and Shi, C. and Doddaballapur, A. and Ong, Y.T. and Wilhelm, K. and Fasse, J.W.D. and Ernst, A. and Kaulich, M. and Husnjak, K. and Boettger, T. and Guenther, S. and Braun, T. and Krüger, M. and Benedito, R. and Dikic, I. and Potente, M.
Abstract:Notch signaling is a core patterning module for vascular morphogenesis that codetermines the sprouting behavior of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood. We found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor. Accordingly, inactivation of USP10 reduced NICD1 abundance and stability and diminished Notch-induced target gene expression in ECs. In mice, the loss of endothelial Usp10 increased vessel sprouting and partially restored the patterning defects caused by ectopic expression of NICD1. Thus, USP10 functions as an NICD1 deubiquitinase that fine-tunes endothelial Notch responses during angiogenic sprouting.
Keywords:HEK293 Cells, Human Umbilical Vein Endothelial Cells, Knockout Mice, Notch1 Receptor, Physiologic Neovascularization, Protein Domains, Protein Stability, Proteolysis, Signal Transduction, Small Interfering RNA, Ubiquitin Thiolesterase, Vascular Endothelium, Animals, Mice
Publisher:American Association for the Advancement of Science
Page Range:188-193
Date:12 April 2019
Official Publication:https://doi.org/10.1126/science.aat0778
PubMed:View item in PubMed

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