Dataset Information

Gain of function notch phenotypes associated with ectopic expression of the Su(H) C-terminal domain illustrate separability of Notch and hairless-mediated activities.

ABSTRACT: The Notch signaling pathway is instrumental for cell fate decisions. Signals from the Notch receptor are transduced by CSL-type DNA-binding proteins. In Drosophila, this protein is named Suppressor of Hairless [Su(H)]. Together with the intracellular domain of the activated Notch receptor ICN, Su(H) assembles a transcriptional activator complex on Notch target genes. Hairless acts as the major antagonist of the Notch signaling pathway in Drosophila by means of the formation of a repressor complex together with Su(H) and several co-repressors. Su(H) is characterized by three domains, the N-terminal domain NTD, the beta-trefoil domain BTD and the C-terminal domain CTD. NTD and BTD bind to the DNA, whereas BTD and CTD bind to ICN. Hairless binds to the CTD, however, to sites different from ICN. In this work, we have addressed the question of competition and availability of Su(H) for ICN and Hairless binding in vivo. To this end, we overexpressed the CTD during fly development. We observed a strong activation of Notch signaling processes in various tissues, which may be explained by an interference of CTD with Hairless corepressor activity. Accordingly, a combined overexpression of CTD together with Hairless ameliorated the effects, unlike Su(H) which strongly enhances repression when overexpressed concomitantly with Hairless. Interestingly, in the combined overexpression CTD accumulated in the nucleus together with Hairless, whereas it is predominantly cytoplasmic on its own.

SUBMITTER: Maier D

PROVIDER: S-EPMC3839874 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gain of function notch phenotypes associated with ectopic expression of the Su(H) C-terminal domain illustrate separability of Notch and hairless-mediated activities.

Maier Dieter D Praxenthaler Heiko H Schulz Adriana A Preiss Anette A

PloS one 20131125 11

The Notch signaling pathway is instrumental for cell fate decisions. Signals from the Notch receptor are transduced by CSL-type DNA-binding proteins. In Drosophila, this protein is named Suppressor of Hairless [Su(H)]. Together with the intracellular domain of the activated Notch receptor ICN, Su(H) assembles a transcriptional activator complex on Notch target genes. Hairless acts as the major antagonist of the Notch signaling pathway in Drosophila by means of the formation of a repressor comple ...[more]

PMID: 24282610

Similar Datasets

Project description:BackgroundThe Notch signaling pathway is fundamental to the regulation of many cell fate decisions in eumetazoans. Not surprisingly, members of this pathway are highly conserved even between vertebrates and invertebrates. There is one notable exception, Hairless, which acts as a general Notch antagonist in Drosophila. Hairless silences Notch target genes by assembling a repressor complex together with Suppressor of Hairless [Su(H)] and the co-repressors Groucho (Gro) and C-terminal binding protein (CtBP). Now with the availability of genomic databases, presumptive Hairless homologues are predicted, however only in insect species. To further our understanding of Hairless structure and function, we have cloned the Hairless gene from Apis mellifera (A.m.H) and characterized its functional conservation in Drosophila.ResultsThe Apis Hairless protein is only one third of the size of the Drosophila orthologue. Interestingly, the defined Suppressor of Hairless binding domain is interrupted by a nonconserved spacer sequence and the N-terminal motif is sufficient for binding. In contrast to Apis Hairless, the Drosophila orthologue contains a large acidic domain and we provide experimental evidence that this acidic domain is necessary to silence Hairless activity in vivo. Despite the dramatic size differences, Apis Hairless binds to the Drosophila Hairless interactors Su(H), Gro, CtBP and Pros26.4. Hence, Apis Hairless assembles a repressor complex with Drosophila components that may have a different topology. Nevertheless, Apis Hairless is sufficient to repress the Notch target gene vestigial in Drosophila. Moreover, it is able to rescue Hairless mutant phenotypes, providing in vivo evidence for its function as a bona fide Notch antagonist.ConclusionThis is the first interspecies-complementation analysis of the Hairless gene. Guided by evolutionary comparisons, we hope to eventually identify all the relevant structural domains and cofactors of Hairless, thereby opening an avenue for further insights into the repressor-complexes that down-regulate Notch signaling also in other, higher eukaryotes.

Dataset Information

Gain of function notch phenotypes associated with ectopic expression of the Su(H) C-terminal domain illustrate separability of Notch and hairless-mediated activities.

Publications

Gain of function notch phenotypes associated with ectopic expression of the Su(H) C-terminal domain illustrate separability of Notch and hairless-mediated activities.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets