The <i>C. elegans</i> homolog of the mammalian tumor suppressor <i>Dep-1/Scc1</i> inhibits EGFR signaling to regulate binary cell fate decisions

Berset, Thomas; Hoier, Erika Fröhli; Hajnal, Alex

doi:10.1101/gad.333505

Cited by 81 publications

(106 citation statements)

References 65 publications

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“…2A-C,E). Furthermore, the expression of egl-17, which in wild-type at the L4 stage specifically marks the descendants of the secondary cell fate lineage, vulC and vulD, (Berset et al, 2005;Burdine et al, 1998), is partially lost in rbr-2(tm3141) animals, correlating with abnormal vulva morphology observed at this stage ( Fig. 2D,E).…”

Section: Rbr-2 Is Required For Secondary Cell Fate Acquisitionmentioning

confidence: 90%

Impaired removal of H3K4 methylation affects cell fate determination and gene transcription

et al. 2016

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Methylation of histone 3 lysine 4 (H3K4) is largely associated with promoters and enhancers of actively transcribed genes and is finely regulated during development by the action of histone methyltransferases and demethylases. H3K4me3 demethylases of the KDM5 family have been previously implicated in development, but how the regulation of H3K4me3 level controls developmental processes is not fully established. Here, we show that the H3K4 demethylase RBR-2, the unique member of the KDM5 family in C. elegans, acts cell-autonomously and in a catalytic-dependent manner to control vulva precursor cells fate acquisition, by promoting the LIN-12/Notch pathway. Using genome-wide approaches, we show that RBR-2 reduces the H3K4me3 level at transcription start sites (TSSs) and in regions upstream of the TSSs, and acts both as a transcription repressor and activator. Analysis of the lin-11 genetic locus, a direct RBR-2 target gene required for vulva precursor cell fate acquisition, shows that RBR-2 controls the epigenetic signature of the lin-11 vulva-specific enhancer and lin-11 expression, providing in vivo evidence that RBR-2 can positively regulate transcription and cell fate acquisition by controlling enhancer activity.

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Section: Rbr-2 Is Required For Secondary Cell Fate Acquisitionmentioning

confidence: 90%

Impaired removal of H3K4 methylation affects cell fate determination and gene transcription

et al. 2016

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“…Tyrosine dephosphorylation of active ErbB receptors can occur through phosphatases, including density-enhanced phosphatase-1 (DEP1) [80] and protein tyrosine phosphatase PTP1B [81]. Dephosphorylation has the capacity to down-regulate activated receptors through abolishment of binding sites for signaling intermediates and adaptor proteins.…”

Section: Signal Attenuationmentioning

confidence: 99%

The epidermal growth factor receptor family: Biology driving targeted therapeutics

Wieduwilt

Moasser

2008

Cell. Mol. Life Sci.

633

503

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The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in regulating cell proliferation, survival, differentiation and migration. The ErbB receptors carry out both redundant and restricted functions in mammalian development and in the maintenance of tissues in the adult mammal. Loss of regulation of the ErbB receptors underlies many human diseases, most notably cancer. Our understanding of the function and complex regulation of these receptors has fueled the development of targeted therapeutic agents for human malignancies in the last 15 years. Here we review the biology of ErbB receptors, including their structure, signaling, regulation, and roles in development and disease, then briefly touch on their increasing roles as targets for cancer therapy.

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“…The DEP-1 receptor tyrosine phosphatase binds to and dephosphorylates activated EGFR. Expression of DEP-1 is repressed by EGFR activation in the primary cells, and is induced by a Notch-independent mechanism in the secondary cells (Berset et al, 2005). The use of parallel mechanisms that restrict EGFR activation in the secondary cells converts the graded activation by the ligand LIN-3 into a binary EGFR-activation response.…”

Section: Inter-relationship Between Egfr and Notch Signalingmentioning

confidence: 99%

Regulating the dynamics of EGF receptor signaling in space and time

2005

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ReviewDevelopment 4018 restricted (Golembo et al., 1999;Neuman-Silberberg and Schupbach, 1993;Simcox et al., 1996;Wasserman and Freeman, 1998), the primary ligand Spitz is broadly expressed (Rutledge et al., 1992). Regulated processing, rather than restricted expression, provides the primary cue for the spatial and temporal activation of the pathway by Spitz. This mode of regulation constrains where and when the active ligand is processed, prevents the inappropriate production of a potent ligand in tissues not requiring activation, and involves controlled intracellular trafficking (see Box 1). The processing of Spitz requires two proteins that are an integral part of EGFR signaling in all Drosophila tissues: Star and Rhomboid (Bier et al., 1990; Kolodkin et al., 1994;Schweitzer et al., 1995). In accordance with their central role in processing, the phenotypes of Drosophila embryos homozygous for mutant alleles of Star or rhomboid are highly similar to those of spitz (Mayer and Nusslein-Volhard, 1988). Rhomboids and EGFR activationThe characterization of the key molecules that process Spitz has provided a deeper understanding of how EGFR activation is spatially and temporally controlled. Like spitz, Star is also broadly expressed in most developmental settings, although in some cases its expression domain is confined (Heberlein and Rubin, 1991). Conversely, the expression of rhomboid is extremely dynamic (Bier et al., 1990), and precedes the appearance of EGFR-induced MAPK activation (dpERK) (Gabay et al., 1997). Ectopic rhomboid expression leads to EGFR activation in a wide range of tissues (Golembo et al., 1996a;Sturtevant et al., 1993), indicating that Rhomboid is the limiting factor and all other components are ubiquitous. Thus, the complex array of enhancers that regulate the rhomboid gene contains the 'blueprint' for the dynamic pattern of EGFR activation throughout Drosophila development. An example of this can be seen in denticle-belt specification, where the expression of rhomboid in defined cell rows determines the position of the future denticle belts in each abdominal segment. Expression of rhomboid is induced in two rows by Hedgehog, and in another row by Serrate, triggering Notch signaling. Conversely, Wingless restricts the domain of rhomboid expression (either directly or indirectly) (Alexandre et al., 1999).Rhomboid is the founding member of a conserved gene family (Wasserman and Freeman, 1998), the function of some of its members being an intramembrane protease (Urban et al., 2001). The highest degree of conservation among this family lies within the transmembrane domains, which contain the catalytic site. Active intramembrane proteases belonging to this family have been identified in species from bacteria to humans (Koonin et al., 2003). In Drosophila, seven members of the family have been identified (Wasserman et al., 2000). Only three have so far been shown to be involved in EGFR signaling. Rhomboid 1 is the cardinal player in this context. Rhomboid 2/BRHO/STET is expressed in the germline ...

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The C. elegans homolog of the mammalian tumor suppressor Dep-1/Scc1 inhibits EGFR signaling to regulate binary cell fate decisions

Abstract: [Keywords: C. elegans; vulval development; EGFR; receptor protein tyrosine phosphatases; tumor suppressor] Supplemental material is available at http://www.genesdev.org.

Cited by 81 publications

References 65 publications

Impaired removal of H3K4 methylation affects cell fate determination and gene transcription

Impaired removal of H3K4 methylation affects cell fate determination and gene transcription

The epidermal growth factor receptor family: Biology driving targeted therapeutics

Regulating the dynamics of EGF receptor signaling in space and time

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