Insensitive is a corepressor for Suppressor of Hairless and regulates Notch signalling during neural development Journal Article
| Authors: | Duan, H.; Dai, Q.; Kavaler, J.; Bejarano, F.; Medranda, G.; Negre, N.; Lai, E. C. |
| Article Title: | Insensitive is a corepressor for Suppressor of Hairless and regulates Notch signalling during neural development |
| Abstract: | The Notch intracellular domain functions as a co-activator for the DNA-binding protein Suppressor of Hairless (Su(H)) to mediate myriad cell fate decisions. Notch pathway activity is balanced by transcriptional repression, mediated by Su(H) in concert with its Drosophila corepressor Hairless. We demonstrate that the Drosophila neural BEN-solo protein Insensitive (Insv) is a nuclear factor that inhibits Notch signalling during multiple peripheral nervous system cell fate decisions. Endogenous Insv was particularly critical when repressor activity of Su(H) was compromised. Reciprocally, ectopic Insv generated several Notch loss-of-function phenotypes, repressed most Notch targets in the E(spl)-C, and opposed Notch-mediated activation of an E(spl)m3-luc reporter. A direct role for Insv in transcriptional repression was indicated by binding of Insv to Su(H), and by strong chromatin immunoprecipitation of endogenous Insv to most E(spl)-C loci. Strikingly, ectopic Insv fully rescued sensory organ precursors in Hairless null clones, indicating that Insv can antagonize Notch independently of Hairless. These data shed first light on the in vivo function for a BEN-solo protein as an Su(H) corepressor in the Notch pathway regulating neural development. © 2011 European Molecular Biology Organization. |
| Keywords: | signal transduction; unclassified drug; dna binding protein; nonhuman; protein domain; protein function; phenotype; notch receptor; cell fate; molecular cloning; regulatory mechanism; chromatin immunoprecipitation; reporter gene; repressor protein; loss of function mutation; peripheral nervous system; regulator protein; corepressor; notch; nerve growth; nuclear factor; ben-solo; insensitive; suppressor of hairless; corepressor protein; protein insensitive; suppressor of hairless protein |
| Journal Title: | EMBO Journal |
| Volume: | 30 |
| Issue: | 15 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2011-07-15 |
| Start Page: | 3120 |
| End Page: | 3133 |
| Language: | English |
| DOI: | 10.1038/emboj.2011.218 |
| PROVIDER: | scopus |
| PMCID: | PMC3160191 |
| PUBMED: | 21765394 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 October 2011" - "CODEN: EMJOD" - "Source: Scopus" |
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