In Drosophila, tissue specific overexpression of both Krz (Kurtz) and Dx (Deltex) results in significant reduction in Notch protein levels and in phenotypes that are reminiscent of Notch loss of function phenotypes. Reduction in Notch protein levels in the presence of overexpressed Kurtz and Deltex is accompanied by significantly higher ubiquitination of Notch (a recombinant HA-tagged ubiquitin was used in these experiments), and Notch is stabilized by treatment with proteasome inhibitors. The identity of the ubiquitin ligase involved in Kurtz:Deltex mediated ubiquitination of Notch has not been determined.