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Citation
Dalton, H.E., Denton, D., Foot, N.J., Ho, K., Mills, K., Brou, C., Kumar, S. (2011). Drosophila Ndfip is a novel regulator of Notch signaling.  Cell Death Differ. 18(7): 1150--1160.
FlyBase ID
FBrf0214123
Publication Type
Research paper
Abstract

In the Drosophila wing, the Nedd4 ubiquitin ligases (E3s), dNedd4 and Su(dx), are important negative regulators of Notch signaling; they ubiquitinate Notch, promoting its endocytosis and turnover. Here, we show that Drosophila Nedd4 family interacting protein (dNdfip) interacts with the Drosophila Nedd4-like E3s. dNdfip expression dramatically enhances dNedd4 and Su(dx)-mediated wing phenotypes and further disrupts Notch signaling. dNdfip colocalizes with Notch in wing imaginal discs and with the late endosomal marker Rab7 in cultured cells. In addition, dNdfip expression in the wing leads to ectopic Notch signaling. Supporting this, expression of dNdfip suppressed Notch(+/-) wing phenotype and knockdown of dNdfip enhanced the Notch(+/-) wing phenotype. The increase in Notch activity by dNdfip is ligand independent as dNdfip expression also suppressed deltex RNAi and Serrate(+/-) wing phenotypes. The opposing effects of dNdfip expression on Notch signaling and its late endosomal localization support a model whereby dNdfip promotes localization of Notch to the limiting membrane of late endosomes allowing for activation, similar to the model previously shown with ectopic Deltex expression. When dNedd4 or Su(dx) are also present, dNdfip promotes their activity in Notch ubiquitination and internalization to the lysosomal lumen for degradation.

PubMed ID
PubMed Central ID
PMC3131964 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Death Differ.
    Title
    Cell Death and Differentiation
    Publication Year
    1994-
    ISBN/ISSN
    1350-9047
    Data From Reference
    Alleles (11)
    Gene Groups (2)
    Genes (13)
    Physical Interactions (6)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (3)
    Experimental Tools (2)
    Transgenic Constructs (6)