Identification of a novel activation domain in the Notch-responsive transcription factor CSL.
CSL is the primary target of the Notch signaling pathway in mammalian cells. It is a DNA binding protein that generally represses transcription in the absence of Notch signaling and activates transcription upon formation of a ternary complex with NICD, the protease-generated intracellular domain of NOTCH: Previous mapping experiments identified the central third of CSL as both necessary and sufficient for DNA binding and activation by NOTCH: Here we show that CSL promotes transcription in 293T cells in the absence of added NICD and that this activity requires both the central domain plus the C-terminal third of the protein. Evidence is presented that argues against a contribution of endogenous NICD and instead supports the possibility that distinct coactivators may directly stimulate the activity of CSL in a cell type-specific manner. This conclusion supports a recent finding that Drosophila CSL (Suppressor of Hairless) can also mediate transcriptional activation in the absence of NOTCH:
Tang
Z
Z
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6145, USA.
Kadesch
T
T
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009841:Oligonucleotides; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors