Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Cell Rep
2016 May 31;159:1920-9. doi: 10.1016/j.celrep.2016.04.070.
Show Gene links
Show Anatomy links
Identification of a Paralog-Specific Notch1 Intracellular Domain Degron.
Broadus MR
,
Chen TW
,
Neitzel LR
,
Ng VH
,
Jodoin JN
,
Lee LA
,
Salic A
,
Robbins DJ
,
Capobianco AJ
,
Patton JG
,
Huppert SS
,
Lee E
.
???displayArticle.abstract???
Upon Notch pathway activation, the receptor is cleaved to release the Notch intracellular domain (NICD), which translocates to the nucleus to activate gene transcription. Using Xenopus egg extracts, we have identified a Notch1-specific destruction signal (N1-Box). We show that mutations in the N1-Box inhibit NICD1 degradation and that the N1-Box is transferable for the promotion of degradation of heterologous proteins in Xenopus egg extracts and in cultured human cells. Mutation of the N1-Box enhances Notch1 activity in cultured human cells and zebrafish embryos. Human cancer mutations within the N1-Box enhance Notch1 signaling in transgenic zebrafish, highlighting the physiological relevance of this destruction signal. We find that binding of the Notch nuclear factor, CSL, to the N1-Box blocks NICD1 turnover. Our studies reveal a mechanism by which degradation of NICD1 is regulated by the N1-Box to minimize stochastic flux and to establish a threshold for Notch1 pathway activation.
Artavanis-Tsakonas,
Notch signaling: cell fate control and signal integration in development.
1999, Pubmed
Artavanis-Tsakonas,
Notch signaling: cell fate control and signal integration in development.
1999,
Pubmed
Blader,
Multiple regulatory elements with spatially and temporally distinct activities control neurogenin1 expression in primary neurons of the zebrafish embryo.
2003,
Pubmed
Chen,
Reconstitution Of β-catenin degradation in Xenopus egg extract.
2014,
Pubmed
,
Xenbase
Chiang,
Identification of a conserved negative regulatory sequence that influences the leukemogenic activity of NOTCH1.
2006,
Pubmed
Chu,
Evidence that C promoter-binding factor 1 binding is required for Notch-1-mediated repression of activator protein-1.
2004,
Pubmed
Fryer,
Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover.
2004,
Pubmed
Fryer,
Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex.
2002,
Pubmed
,
Xenbase
Gupta-Rossi,
Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor.
2001,
Pubmed
Harima,
Oscillatory links of Fgf signaling and Hes7 in the segmentation clock.
2013,
Pubmed
Ilagan,
Real-time imaging of notch activation with a luciferase complementation-based reporter.
2011,
Pubmed
Kopan,
The canonical Notch signaling pathway: unfolding the activation mechanism.
2009,
Pubmed
Kovall,
Mechanistic insights into Notch receptor signaling from structural and biochemical studies.
2010,
Pubmed
Lewis,
Notch signaling, the segmentation clock, and the patterning of vertebrate somites.
2009,
Pubmed
Liu,
The extracellular domain of Notch2 increases its cell-surface abundance and ligand responsiveness during kidney development.
2013,
Pubmed
Malyukova,
The tumor suppressor gene hCDC4 is frequently mutated in human T-cell acute lymphoblastic leukemia with functional consequences for Notch signaling.
2007,
Pubmed
Mo,
Integrin-linked kinase controls Notch1 signaling by down-regulation of protein stability through Fbw7 ubiquitin ligase.
2007,
Pubmed
Moretti,
Ubiquitinations in the notch signaling pathway.
2013,
Pubmed
Nam,
Structural requirements for assembly of the CSL.intracellular Notch1.Mastermind-like 1 transcriptional activation complex.
2003,
Pubmed
O'Neil,
FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors.
2007,
Pubmed
Oberg,
The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog.
2001,
Pubmed
Palermo,
Acetylation controls Notch3 stability and function in T-cell leukemia.
2012,
Pubmed
Qiu,
Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligase.
2000,
Pubmed
Skaar,
Mechanisms and function of substrate recruitment by F-box proteins.
2013,
Pubmed
Tamura,
Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H).
1995,
Pubmed
Thompson,
The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia.
2007,
Pubmed
Tsunematsu,
Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development.
2004,
Pubmed
Vasquez-Del Carpio,
Assembly of a Notch transcriptional activation complex requires multimerization.
2011,
Pubmed
Weng,
Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia.
2004,
Pubmed
Wu,
SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation.
2001,
Pubmed
Yaron,
Juxtacrine signaling is inherently noisy.
2014,
Pubmed
Yeo,
Fluorescent protein expression driven by her4 regulatory elements reveals the spatiotemporal pattern of Notch signaling in the nervous system of zebrafish embryos.
2007,
Pubmed
