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Deubiquitinase USP10 regulates Notch signaling in the endothelium.

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Title: Deubiquitinase USP10 regulates Notch signaling in the endothelium.
Authors: 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, R., Dikic, I., Potente, M.
Source: Science (pre-March 2025). 4/12/2019, Vol. 364 Issue 6436, p188-193. 6p. 4 Diagrams.
Subjects: Endothelium, Notch signaling pathway, Endothelial cells, Ubiquitin, Peptidase
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. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Deubiquitinase USP10 regulates Notch signaling in the endothelium.
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  Data: <searchLink fieldCode="AR" term="%22Lim%2C+R%2E%22">Lim, R.</searchLink><br /><searchLink fieldCode="AR" term="%22Sugino%2C+T%2E%22">Sugino, T.</searchLink><br /><searchLink fieldCode="AR" term="%22Nolte%2C+H%2E%22">Nolte, H.</searchLink><br /><searchLink fieldCode="AR" term="%22Andrade%2C+J%2E%22">Andrade, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Zimmermann%2C+B%2E%22">Zimmermann, B.</searchLink><br /><searchLink fieldCode="AR" term="%22Shi%2C+C%2E%22">Shi, C.</searchLink><br /><searchLink fieldCode="AR" term="%22Doddaballapur%2C+A%2E%22">Doddaballapur, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Ong%2C+Y%2E+T%2E%22">Ong, Y. T.</searchLink><br /><searchLink fieldCode="AR" term="%22Wilhelm%2C+K%2E%22">Wilhelm, K.</searchLink><br /><searchLink fieldCode="AR" term="%22Fasse%2C+J%2E+W%2E+D%2E%22">Fasse, J. W. D.</searchLink><br /><searchLink fieldCode="AR" term="%22Ernst%2C+A%2E%22">Ernst, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Kaulich%2C+M%2E%22">Kaulich, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Husnjak%2C+K%2E%22">Husnjak, K.</searchLink><br /><searchLink fieldCode="AR" term="%22Boettger%2C+T%2E%22">Boettger, T.</searchLink><br /><searchLink fieldCode="AR" term="%22Guenther%2C+S%2E%22">Guenther, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Braun%2C+T%2E%22">Braun, T.</searchLink><br /><searchLink fieldCode="AR" term="%22Krüger%2C+M%2E%22">Krüger, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Benedito%2C+R%2E%22">Benedito, R.</searchLink><br /><searchLink fieldCode="AR" term="%22Dikic%2C+I%2E%22">Dikic, I.</searchLink><br /><searchLink fieldCode="AR" term="%22Potente%2C+M%2E%22">Potente, M.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 4/12/2019, Vol. 364 Issue 6436, p188-193. 6p. 4 Diagrams.
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  Data: <searchLink fieldCode="DE" term="%22Endothelium%22">Endothelium</searchLink><br /><searchLink fieldCode="DE" term="%22Notch+signaling+pathway%22">Notch signaling pathway</searchLink><br /><searchLink fieldCode="DE" term="%22Endothelial+cells%22">Endothelial cells</searchLink><br /><searchLink fieldCode="DE" term="%22Ubiquitin%22">Ubiquitin</searchLink><br /><searchLink fieldCode="DE" term="%22Peptidase%22">Peptidase</searchLink>
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  Label: Abstract
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  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=135852401
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        Value: 10.1126/science.aat0778
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        Text: English
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        PageCount: 6
        StartPage: 188
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      – SubjectFull: Endothelium
        Type: general
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