DELTEX ACTS AS A POSITIVE REGULATOR OF NOTCH SIGNALING THROUGH INTERACTIONS WITH THE NOTCH ANKYRIN REPEATS

We present a molecular and genetic analysis which elucidates the role of deltex in the Notch signaling pathway, Using the yeast 'interaction trap' assay, we define the protein regions responsible for heterotypi c interactions between Deltex and the intracellular domain of Notch as well as uncover homotypic interaction among Deltex molecules. The fun ction of the Deltex-Notch interaction domains is examined by in vivo e xpression studies. Taken together, data from overexpression of Deltex fragments and from studies of physical interactions between Deltex and Notch, suggest that Deltex positively regulates the Notch pathway thr ough interactions with the Notch ankyrin repeats, Experiments involvin g cell cultures indicate that the Deltex-Notch interaction prevents th e cytoplasmic retention of the Suppressor of Hairless protein, which o therwise is sequestered in the cytoplasm via association with the Notc h ankyrin repeats and translocates to the nucleus when Notch binds to its ligand Delta. On the basis of these findings, we propose a model w herein Deltex regulates Notch activity by antagonizing the interaction between Notch and Suppressor of Hairless.