Structures of CSL, Notch and Mastermind proteins: piecing together an active transcription complex

Notch signaling mediates communication between cells, and is essential for proper cell fate decisions in the developing embryo and the adult organism. Signaling initiates proteolytic release of the receptor Notch from the membrane, whereupon the intracellular portion of Notch (NotchIC) localizes to the nucleus and engages the DNA-binding transcription factor CSL. CSL is required for both repression and activation of Notch target genes, and is the focal point of a transcriptional switch, mediating interactions with transcriptional coregulators. Activation of transcription requires corepressor displacement from CSL by NotchIC and the recruitment of the transcriptional coactivator Mastermind to the complex. Several recently determined and exciting structures of CSL, NotchIC, and an active transcription complex composed of CSL, NotchIC and Mastermind have revealed new insights into transcriptional regulation in the Notch pathway.