Notch Targets and Their Regulation

Bray, Sarah; Bernard, Fred

doi:10.1016/s0070-2153(10)92008-5

Cited by 141 publications

(114 citation statements)

References 153 publications

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“…Interestingly, whereas Notch1 ICD performs well on paired CSL binding sites, Notch3 ICD activity is more amenable to binding CSL motifs adjacent to binding sites for zinc-finger transcription factors (Ong et al, 2006). The spacing of multimerized binding sites within target genes is also important for activation (for a review, see Bray and Bernard, 2010). The ability of Notch ICDs to form dimers might also influence the repertoire of activated genes by restricting the response to dimeric CSL binding sites (Cave et al, 2005), although structural analysis of the dimeric Notch ICD complex suggests that a flexibility in spacer length can be accommodated (Arnett et al, 2010).…”

Section: Reviewmentioning

confidence: 99%

Notch signaling: simplicity in design, versatility in function

2011

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Notch signaling is evolutionarily conserved and operates in many cell types and at various stages during development. Notch signaling must therefore be able to generate appropriate signaling outputs in a variety of cellular contexts. This need for versatility in Notch signaling is in apparent contrast to the simple molecular design of the core pathway. Here, we review recent studies in nematodes, Drosophila and vertebrate systems that begin to shed light on how versatility in Notch signaling output is generated, how signal strength is modulated, and how cross-talk between the Notch pathway and other intracellular signaling systems, such as the Wnt, hypoxia and BMP pathways, contributes to signaling diversity.Key words: Cis-inhibition, Delta-like, Signaling diversity, Jagged, Notch, Notch intracellular domain Introduction Cells need to sense cues from their extracellular environment and integrate this information into appropriate developmental or physiological responses. Although there are a number of mechanisms that relay information from the exterior of the cell to the interior, a relatively small set of highly evolutionarily conserved signaling pathways stand out as playing particularly crucial roles in this transmission of information. In this roster of 'elite' intracellular signaling mechanisms are the Wnt pathway, the sonic hedgehog (Shh) pathway, the bone morphogenetic protein/transforming growth factor  (BMP/TGF) pathway, phosphatidylinositol 3-kinase/thymoma viral proto-oncogene (PI3K/AKT) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and, the subject of this review, the Notch signaling pathway. Each of these pathways converts information about the concentration of extracellular ligands into specific transcriptional responses in the nucleus. In most cases, the signaling mechanism consists of the 'core' signaling pathway, i.e. the minimal set of protein components required for transducing the signal, and a more elaborate set of 'auxiliary' proteins, which, in various ways, impinge upon the core pathway and modify the signal but are not intrinsically necessary for relaying the signal.Among these highly conserved pathways (Gazave et al., 2009;Richards and Degnan, 2009), the Notch signaling pathway scores highly with regard to simplicity in molecular design, as it contains only a small number of core signaling components (Fig. 1). Despite this, Notch signaling affects cell differentiation decisions not only across a wide spectrum of metazoan species, but also across a broad range of cell types in a single organism and at different steps during cell lineage progression. The pleiotropic actions of Notch in different cell types and organs have recently been reviewed and are summarized in Table 1. In keeping with its important role in many cell types, the mutation of Notch genes leads to diseases in various organs and tissues (Table 2). These studies highlight the fact that the Notch pathway must be able to elicit appropriate responses in many spatially and temporally...

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Section: Reviewmentioning

confidence: 99%

Notch signaling: simplicity in design, versatility in function

2011

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“…Interestingly, Notch has both cellautonomous and non-cell-autonomous effects on mitotic activity, which it can either promote or suppress depending on the cellular context. Although many aspects of Notch signaling in proliferation and apoptosis remain poorly understood, its potential to link these events to differentiation might be of particular relevance to dysproliferative states, including cancer (Bray, 2006;Fiúza and Arias, 2007;Bray and Bernard, 2010).…”

Section: Proliferation and Apoptosismentioning

confidence: 99%

Notch signaling at a glance

Hori

Sen

Artavanis‐Tsakonas

2013

Journal of Cell Science

455

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Cell–cell interactions define a quintessential aspect of multicellular development. Metazoan morphogenesis depends on a handful of fundamental, conserved cellular interaction mechanisms, one of which is defined by the Notch signaling pathway. Signals transmitted through the Notch surface receptor have a unique developmental role: Notch signaling links the fate of one cell with that of a cellular neighbor through physical interactions between the Notch receptor and the membrane-bound ligands that are expressed in an apposing cell. The developmental outcome of Notch signals is strictly dependent on the cellular context and can influence differentiation, proliferation and apoptotic cell fates. The Notch pathway is conserved across species (Artavanis-Tsakonas et al., 1999; Bray, 2006; Kopan and Ilagan, 2009). In humans, Notch malfunction has been associated with a diverse range of diseases linked to changes in cell fate and cell proliferation including cancer (Louvi and Artavanis-Tsakonas, 2012). In this Cell Science at a Glance article and the accompanying poster we summarize the molecular biology of Notch signaling, its role in development and its relevance to disease.

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“…The resultant NICD/CSL complex activates Notch-target genes (Bray and Bernard, 2010). ( Baxendale et al, 2004;van Eeden et al, 1996;Hernandez-Lagunas et al, 2005;Lee and Roy, 2006;Mercader et al, 2006;Wilm and Solnica-Krezel, 2005) Mouse: Failure to elaborate placental labyrinth layer 8,9 .…”

Section: Interplay With Notch Signallingmentioning

confidence: 99%

The Prdm family: expanding roles in stem cells and development

2012

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SummaryMembers of the Prdm family are characterized by an Nterminal PR domain that is related to the SET methyltransferase domain, and multiple zinc fingers that mediate sequence-specific DNA binding and protein-protein interactions. Prdm factors either act as direct histone methyltransferases or recruit a suite of histone-modifying enzymes to target promoters. In this way, they function in many developmental contexts to drive and maintain cell state transitions and to modify the activity of developmental signalling pathways. Here, we provide an overview of the structure and function of Prdm family members and discuss the roles played by these proteins in stem cells and throughout development.

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Notch Targets and Their Regulation

Cited by 141 publications

References 153 publications

Notch signaling: simplicity in design, versatility in function

Notch signaling: simplicity in design, versatility in function

Notch signaling at a glance

The Prdm family: expanding roles in stem cells and development

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