C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling

Abstract Since the generation of a mouse strain conditionally expressing the active intracellular domain of Notch1 (N1ICD), many laboratories have exploited this model (RosaN1-ICD) to assess the impact of constitutive Notch1 signalling activation in normal and pathological processes. It should be un...

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Autores principales:	Jennifer Blain, Jessily Bédard, Maureen Thompson, François-Michel Boisvert, Marie-Josée Boucher
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b7a8f7f361f42c4a3eb461009c92896
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spelling	oai:doaj.org-article:3b7a8f7f361f42c4a3eb461009c928962021-12-02T11:53:12ZC-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling10.1038/s41598-017-05119-02045-2322https://doaj.org/article/3b7a8f7f361f42c4a3eb461009c928962017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05119-0https://doaj.org/toc/2045-2322Abstract Since the generation of a mouse strain conditionally expressing the active intracellular domain of Notch1 (N1ICD), many laboratories have exploited this model (RosaN1-ICD) to assess the impact of constitutive Notch1 signalling activation in normal and pathological processes. It should be underscored that Cre-recombination leads to the expression of a C-terminally truncated form of N1ICD (N1ICDdC) in the RosaN1-ICD mutant mice. Given that no studies were undertaken to delineate whether deletion of this region leaves intact N1ICD function, stable cell lines with single targeted integration of inducible N1ICD and N1ICDdC were generated. We found that C-terminal deletion of N1ICD stabilized the protein but did not promote the activity of Notch responsive promoters. Furthermore, despite higher expression levels, N1ICDdC failed to phenocopy N1ICD in the promotion of anchorage-independent growth. Our results thus suggest that the C-terminal region of N1ICD plays a role in shaping the Notch response. Therefore, it should be taken into consideration that N1ICD is truncated when interpreting phenotypes of RosaN1-ICD mutant mice.Jennifer BlainJessily BédardMaureen ThompsonFrançois-Michel BoisvertMarie-Josée BoucherNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jennifer Blain Jessily Bédard Maureen Thompson François-Michel Boisvert Marie-Josée Boucher C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling
description	Abstract Since the generation of a mouse strain conditionally expressing the active intracellular domain of Notch1 (N1ICD), many laboratories have exploited this model (RosaN1-ICD) to assess the impact of constitutive Notch1 signalling activation in normal and pathological processes. It should be underscored that Cre-recombination leads to the expression of a C-terminally truncated form of N1ICD (N1ICDdC) in the RosaN1-ICD mutant mice. Given that no studies were undertaken to delineate whether deletion of this region leaves intact N1ICD function, stable cell lines with single targeted integration of inducible N1ICD and N1ICDdC were generated. We found that C-terminal deletion of N1ICD stabilized the protein but did not promote the activity of Notch responsive promoters. Furthermore, despite higher expression levels, N1ICDdC failed to phenocopy N1ICD in the promotion of anchorage-independent growth. Our results thus suggest that the C-terminal region of N1ICD plays a role in shaping the Notch response. Therefore, it should be taken into consideration that N1ICD is truncated when interpreting phenotypes of RosaN1-ICD mutant mice.
format	article
author	Jennifer Blain Jessily Bédard Maureen Thompson François-Michel Boisvert Marie-Josée Boucher
author_facet	Jennifer Blain Jessily Bédard Maureen Thompson François-Michel Boisvert Marie-Josée Boucher
author_sort	Jennifer Blain
title	C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling
title_short	C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling
title_full	C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling
title_fullStr	C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling
title_full_unstemmed	C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling
title_sort	c-terminal deletion of notch1 intracellular domain (n1icd) increases its stability but does not amplify and recapitulate n1icd-dependent signalling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3b7a8f7f361f42c4a3eb461009c92896
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C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling

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