High impact information on dx

• Su(H) exhibits numerous allele-specific genetic interactions with Notch as well as with Delta, deltex, and mastermind [1].
• Finally, blocking the N transportation from the plasma membrane to the late-endosome by a dominant-negative form of Rab5 inhibited the Dx-mediated activation of N signaling, suggesting that the accumulation of N in the late-endosome was required for the Dx-mediated Su(H)-independent N signaling [2].
• Drosophila deltex mediates suppressor of Hairless-independent and late-endosomal activation of Notch signaling [2].
• Notch (N) signaling is an evolutionarily conserved mechanism that regulates many cell-fate decisions. deltex (dx) encodes an E3-ubiquitin ligase that binds to the intracellular domain of N and positively regulates N signaling [2].
• Consistent with this, the dx gene was required for the presence of N in the endocytic vesicles [2].

Biological context of dx

• We show that the loss of sensory organs associated with this phenotype results from a constitutive activation of a Deltex-dependent Notch-signaling event [3].
• However, when the same mutant was fused to a heterologous dimerization domain (Glutathione-S-Transferase), the chimeric protein had normal Deltex activity [4].
• Down-regulation of Notch target gene expression by Suppressor of deltex [5].
• One positive regulator of Notch is Deltex, a cytoplasmic, zinc finger domain protein, which binds to the intracellular domain of Notch [6].

Anatomical context of dx

• We rule out models by which Su(dx) downregulates Notch through modulating Deltex or by limiting the adherens junction accumulation of Notch [7].
• We previously reported that overexpression of Dx results in the stabilization of Notch in late endosomes [8].

Associations of dx with chemical compounds

• Here, we found that three motifs in Dx, a region that binds to Notch, a proline-rich motif and a RING-H2 finger, were required for this stabilization, although the relative activity of these variants in this assay did not always correspond to the severity of the rough-eye phenotype [8].

Regulatory relationships of dx

• The Drosophila deltex gene regulates Notch signaling in a positive manner, and its gene product physically interacts with the intracellular domain of Notch through its N-terminal domain [4].

Other interactions of dx

• This activity, mediated by Deltex (Dx), represses neural fate and is antagonized by elements of the Wingless (Wg)-signaling cascade to allow alternative cell fate choices [3].
• We have determined the solution structure and dynamics of a pair of WW domains (WW3-4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling [9].
• Prior genetic studies have suggested a functional relationship between the product of the deltex gene and those of three of the so-called "neurogenic" loci, Notch, Delta and mastermind [10].

References