Small GTPase RhoE/Rnd3 is a critical regulator of Notch1 signaling.

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Serval ID
serval:BIB_D2AD80A2F450
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Small GTPase RhoE/Rnd3 is a critical regulator of Notch1 signaling.
Journal
Cancer Research
Author(s)
Zhu Z., Todorova K., Lee K.K., Wang J., Kwon E., Kehayov I., Kim H.G., Kolev V., Dotto G.P., Lee S.W., Mandinova A.
ISSN
1538-7445 (Electronic)
ISSN-L
0008-5472
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
74
Number
7
Pages
2082-2093
Language
english
Abstract
Aberrations of Notch signaling have been implicated in a variety of human cancers. Oncogenic mutations in NOTCH1 are common in human T-cell leukemia and lymphomas. However, loss-of-function somatic mutations in NOTCH1 arising in solid tumors imply a tumor suppressor function, which highlights the need to understand Notch signaling more completely. Here, we describe the small GTPase RhoE/Rnd3 as a downstream mediator of Notch signaling in squamous cell carcinomas (SCC) that arise in skin epithelia. RhoE is a transcriptional target of activated Notch1, which is attenuated broadly in SCC cells. RhoE depletion suppresses Notch1-mediated signaling in vitro, rendering primary keratinocytes resistant to Notch1-mediated differentiation and thereby favoring a proliferative cell fate. Mechanistic investigations indicated that RhoE controls a key step in Notch1 signaling by mediating nuclear translocation of the activated portion of Notch1 (N1IC) through interaction with importins. Our results define RhoE as a Notch1 target that is essential for recruitment of N1IC to the promoters of Notch1 target genes, establishing a regulatory feedback loop in Notch1 signaling. This molecular circuitry may inform distinct cell fate decisions to Notch1 in epithelial tissues, where carcinomas such as SCC arise. Cancer Res; 74(7); 2082-93. ©2014 AACR.
Pubmed
Web of science
Open Access
Yes
Create date
08/05/2014 8:36
Last modification date
20/08/2019 15:52
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