Crosstalk between the EGFR and other signalling pathways at the level of the global transcriptional corepressor Groucho/TLE

Hasson, Peleg; Paroush, Ze’ev

doi:10.1038/sj.bjc.6603019

Cited by 65 publications

(63 citation statements)

References 32 publications

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“…The genetic interaction between dMyc and Gro fits well with previously reported genetic interactions between NotchGro and EGF-Gro (15). We find that dMyc also interacts genetically with EGF and Notch, leading to disruptions in neurogenesis.…”

Section: Dmyc Interacts Genetically With Egf Receptor and Notch Duringsupporting

confidence: 75%

“…2D). These mutants also show neuroblast hyperplasia ( Another patterning/fate determination process governed by EGF and Notch signaling is the specification of mesothoracic sensory bristles in the peripheral nervous system (PNS) (13)(14)(15). Similar to our findings during neuroblast development, we find that loss of Gro or dMyc overexpression phenocopies activation of the EGF pathway, whereas loss of dMyc expression or overexpression of Gro phenocopies activated Notch signaling (SI Fig.…”

supporting

confidence: 76%

“…Signaling. Gro is a downstream transducer of several signaling pathways and was placed at the crossroads of the Notch and EGF signaling pathways during patterning of the Drosophila nervous system, where EGF-induced site-specific phosphorylation of Gro attenuates it repression activity (13)(14)(15). During embryonic stage 9, the CNS matures in three bilaterally symmetrical longitudinal rows of neuroblasts (16), with the homeobox transcription factors, Vnd, Ind, and Msh, specifying the medial (ventral), intermediate, and lateral rows, respectively ( Fig.…”

mentioning

confidence: 99%

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A Myc–Groucho complex integrates EGF and Notch signaling to regulate neural development

Orian

Delrow

Rosales-Nieves

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Integration of patterning cues via transcriptional networks to coordinate gene expression is critical during morphogenesis and misregulated in cancer. Using DNA adenine methyltransferase (Dam)ID chromatin profiling, we identified a protein-protein interaction between the Drosophila Myc oncogene and the Groucho corepressor that regulates a subset of direct dMyc targets. Most of these shared targets affect fate or mitosis particularly during neurogenesis, suggesting the dMyc-Groucho complex may coordinate fate acquisition with mitotic capacity during development. We find an antagonistic relationship between dMyc and Groucho that mimics the antagonistic interactions found for EGF and Notch signaling: dMyc is required to specify neuronal fate and enhance neuroblast mitosis, whereas Groucho is required to maintain epithelial fate and inhibit mitosis. Our results suggest that the dMyc-Groucho complex defines a previously undescribed mechanism of Myc function and may serve as the transcriptional unit that integrates EGF and Notch inputs to regulate early neuronal development.neurogenesis ͉ Drosophila ͉ stem cell ͉ cell fate ͉ mitosis

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Section: Dmyc Interacts Genetically With Egf Receptor and Notch Duringsupporting

confidence: 75%

supporting

confidence: 76%

mentioning

confidence: 99%

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A Myc–Groucho complex integrates EGF and Notch signaling to regulate neural development

Orian

Delrow

Rosales-Nieves

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Some, like lola and spen, have been implicated previously in Notch signaling and are thought to antagonize the Notch pathway (FerresMarco et al 2006;Doroquez et al 2007). Others, such as lilliputian and tramtrack, are known to have interactions with other pathways, such as the Ras and ecdysteroid pathways, that are known to influence Notch signaling (see above) (Sundaram 2005;Hasson and Paroush 2006). We also identified genes encoding many largely uncharacterized proteins including CG9650, a zinc-finger-containing putative transcription factor that has been implicated in axon guidance in the embryo (McGovern et al 2003).…”

Section: Resultsmentioning

confidence: 99%

A Screen for Modifiers of Notch Signaling Uncovers Amun, a Protein With a Critical Role in Sensory Organ Development

et al. 2009

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Notch signaling is an evolutionarily conserved pathway essential for many cell fate specification events during metazoan development. We conducted a large-scale transposon-based screen in the developing Drosophila eye to identify genes involved in Notch signaling. We screened 10,447 transposon lines from the Exelixis collection for modifiers of cell fate alterations caused by overexpression of the Notch ligand Delta and identified 170 distinct modifier lines that may affect up to 274 genes. These include genes known to function in Notch signaling, as well as a large group of characterized and uncharacterized genes that have not been implicated in Notch pathway function. We further analyze a gene that we have named Amun and show that it encodes a protein that localizes to the nucleus and contains a putative DNA glycosylase domain. Genetic and molecular analyses of Amun show that altered levels of Amun function interfere with cell fate specification during eye and sensory organ development. Overexpression of Amun decreases expression of the proneural transcription factor Achaete, and sensory organ loss caused by Amun overexpression can be rescued by coexpression of Achaete. Taken together, our data suggest that Amun acts as a transcriptional regulator that can affect cell fate specification by controlling Achaete levels.

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“…In bone remodeling, however, the roles of Pax6 remain to be fully defined, although MITF mutant mice show defects in retinal development and osteoclastogenesis (14). One of the molecular mechanisms by which a family of Pax transcription factors function as a repressor can be understood by altering the structure of transcriptional machinery assembled with a Grouch (Grg)-related co-repressor (28). Indeed, Grg/TLE (Groucho/ transducin-like enhancer of split) family protein functions as a modifying factor for the regulation of bone development when it interacts with Runx2, a crucial factor for osteoblasts in vivo (29).…”

mentioning

confidence: 99%

The Paired-box Homeodomain Transcription Factor Pax6 Binds to the Upstream Region of the TRAP Gene Promoter and Suppresses Receptor Activator of NF-κB Ligand (RANKL)-induced Osteoclast Differentiation

Kogawa¹,

Hisatake

Atkins

et al. 2013

Journal of Biological Chemistry

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Background: Negative regulation of osteoclast differentiation is critical for suppression of pathological bone destruction. Results: Pax6 is induced by RANKL in osteoclasts and attenuates osteoclast differentiation via blocking TRAP gene expression. Conclusion: Pax6 functions together with its co-receptor to suppress TRAP gene expression and osteoclastogenesis. Significance: This study provides a new aspect for investigating the molecular targets linked to physiological bone resorption.

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Crosstalk between the EGFR and other signalling pathways at the level of the global transcriptional corepressor Groucho/TLE

Cited by 65 publications

References 32 publications

A Myc–Groucho complex integrates EGF and Notch signaling to regulate neural development

A Myc–Groucho complex integrates EGF and Notch signaling to regulate neural development

A Screen for Modifiers of Notch Signaling Uncovers Amun, a Protein With a Critical Role in Sensory Organ Development

The Paired-box Homeodomain Transcription Factor Pax6 Binds to the Upstream Region of the TRAP Gene Promoter and Suppresses Receptor Activator of NF-κB Ligand (RANKL)-induced Osteoclast Differentiation

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