| A novel notch protein , N2N , targeted by neutrophil elastase and implicated in hereditary neutropenia . ^^^ We utilized a modified yeast two hybrid system and identified a new , widely expressed gene , N2N , whose product is homologous to Notch 2 , that interacts with neutrophil elastase . ^^^ Neutrophil elastase cleaves N2N within EGF repeats in vitro and in living cells , but the C terminal domain retards proteolysis . ^^^ Disease causing mutations of neutrophil elastase disrupt the interaction with N2N , impair proteolysis of N2N and Notch 2 , and interfere with Notch 2 signaling , suggesting defective proteolysis of an inhibitory form of Notch as an explanation for the alternate switching of cell fates characteristic of hereditary neutropenia . . ^^^ |