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Notch receptor-mediated signaling is one of a few highly conserved developmental signaling pathways that are crucial for cell fate determination.This pathway also has been implicated in tumorigenesis, since aberrant Notch activities are associated with a growing number of hematological and epithelial cancers.Notch signaling is tightly regulated by unclear mechanisms, and aberrant Notch signaling (i.e., either abnormally increased or deficient activities) results in disregulation of normal cellular processes.Previously, we determined that the mastermindlike (MAML) family of transcriptional co-activators is essential for Notch-induced transcriptional events: the three family members form ternary complexes with Notch and the transcription factor CSL in the nucleus, thereby activating transcription of specific target genes.However, factors in addition to the core MAML/Notch/CSL complex that participate in transcriptional events are less characterized.To further investigate the regulation of the Notch pathway, we have initiated studies to identify its novel regulators and their specific functions on Notch-mediated cellular processes.These studies will provide significant insights into transcriptional and epigenetic regulation of Notch signaling, in addition to identifying strategies to manipulate Notch signaling in both normal and cancerous cells.