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oai:repisalud.isciii.es:20.500.12105/96852024-09-27T07:57:40Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Lim, R author Sugino, T author Nolte, H author Andrade, J author Zimmermann, B author Shi, C author Doddaballapur, A author Ong, Y T author Wilhelm, K author Fasse, J W D author Ernst, A author Kaulich, M author Husnjak, K author Boettger, T author Guenther, S author Braun, T author Krüger, M author Benedito, Rui author Dikic, I author Potente, M author 2019-04 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. Science. 2019; 364(6436):188-193 http://hdl.handle.net/20.500.12105/9685 30975888 10.1126/science.aat0778 1095-9203 Science (New York, N.Y.) Deubiquitinase USP10 regulates Notch signaling in the endothelium