ArticleBMC biology2023
The meaning of ubiquitylation of the DSL ligand Delta for the development of Drosophila.
Article in BMC biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Article
- Neuralized-like proteins differentially activate Notch ligands.EMBO reports · 2025Article
- The intracellular domains of the DSL ligands Serrate and Delta provide different activities.Cell communication and signaling : CCS · 2025Article
- Quantifying bristle cell organization inbioRxiv : the preprint server for biology · 2025Article
- An in vivo screen identifies diverse domains that can act as force-dependent proteolytic switches for Notch activation.Science signaling · 2025Article
- Article
- Article
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7 authors.
Funding
Abstract
backgroundUbiquitylation (ubi) of the intracellular domain of the Notch ligand Delta (Dl) by the E3 ligases Neuralized (Neur) and Mindbomb1 (Mib1) on lysines (Ks) is thought to be essential for the its signalling activity. Nevertheless, we have previously shown that DlK2R-HA, a Dl variant where all Ks in its intracellular domain (ICD) are replaced by the structurally similar arginine (R), still possess weak activity if over-expressed. This suggests that ubi is not absolutely required for Dl signalling. However, it is not known whether the residual activity of DlK2R-HA is an effect of over-expression and, if not, whether DlK2R can provide sufficient activity for the whole development of Drosophila.
resultsTo clarify these issues, we generated and analysed Dl
conclusionsOur results indicate that Dl can activate the Notch pathway without ubi of its ICD. It signals via three modes. Ubi is specifically required for the Mib1-dependent processes and the adjustment of cis-inhibition. In contrast to Mib1, Neur can efficiently activate Dl without ubi. Neur probably acts as an endocytic co-adapter in addition to its role as E3 ligase. Endocytosis, regulated in a ubi-dependent or ubi-independent manner is required for signalling and also suppression of cis-inhibition. The findings clarify the role of ubi of the ligands during Notch signalling.
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