Universität zu Köln

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., Krueger, M., Benedito, R., Dikic, I. and Potente, M. (2019). Deubiquitinase USP10 regulates Notch signaling in the endothelium. Science, 364 (6436). S. 188 - 221. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1095-9203

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lim, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sugino, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Andrade, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmermann, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shi, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Doddaballapur, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ong, Y. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilhelm, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fasse, J. W. D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ernst, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaulich, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Husnjak, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boettger, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Guenther, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Benedito, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dikic, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Potente, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-150786
DOI:	10.1126/science.aat0778
Journal or Publication Title:	Science
Volume:	364
Number:	6436
Page Range:	S. 188 - 221
Date:	2019
Publisher:	AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication:	WASHINGTON
ISSN:	1095-9203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL BEHAVIOR; ACTIVATION; ANGIOGENESIS; PROTEINS; DLL4; EFFICIENT; VEGF Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15078