Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/9685
Título
Deubiquitinase USP10 regulates Notch signaling in the endothelium
Autor(es)
Lim, R | Sugino, T | Nolte, H | Andrade, J | Zimmermann, B | Shi, C | Doddaballapur, A | Ong, Y T | Wilhelm, K | Fasse, J W D | Ernst, A | Kaulich, M | Husnjak, K | Boettger, T | Guenther, S | Braun, T | Krüger, M | Benedito, Rui CNIC | Dikic, I | Potente, M
Fecha de publicación
2019-04
Cita
Science. 2019; 364(6436):188-193
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Animals | Endothelium, Vascular | HEK293 Cells | Human Umbilical Vein Endothelial Cells | Humans | Mice | Mice, Knockout | Neovascularization, Physiologic | Protein Domains | Protein Stability | RNA, Small Interfering | Receptor, Notch1 | Signal Transduction | Ubiquitin Thiolesterase | Proteolysis
Versión en línea
DOI
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