HUMAN DELTEX IS A CONSERVED REGULATOR OF NOTCH SIGNALING

A fundamental cell-fate control mechanism regulating multicellular dev elopment is defined by the Notch-signalling pathway(1). Developmental and genetic studies of wild type and activated Notch-receptor expressi on in diverse organisms suggest that Notch plays a general role in dev elopment by governing the ability of undifferentiated precursor cells to respond to specific signals(1,2). Notch signalling has been conserv ed throughout evolution and controls the differentiation of a broad sp ectrum of cell types during development(1-3). Genetic studies in Droso phila have led to the identification of several components of the Notc h pathway(1). Two of the positive regulators of the pathway are encode d by the suppressor of hairless [Su(H)] and deltex (dx) genes(5-8). Dr osophila dr encodes a ubiquitous, novel cytoplasmic protein of unknown biochemical function(9). We have cloned a human deltex homologue and characterized it in parallel with its Drosophila counterpart in bioche mical assays to assess deltex function. Both human and Drosophila delt ex bind to Notch across species and carry putative Shy-binding domains . Using the yeast interaction trap system, we find that Drosophila and human deltex bind to the human SH3-domain containing protein Grb2 (re f. 10). Results from two different reporter assays allow us for the fi rst time to associate deltex with Notch-dependent transcriptional even ts. We present evidence linking deltex to the modulation of basic heli x-loop-helix (bHLH) transcription factor activity.