p300 acts as a transcriptional coactivator for mammalian Notch-1.
Notch-1 belongs to a family of transmembrane receptor proteins that direct the decisions as to various cell fates. After ligand binding, a proteolytic cleavage step occurs and the intracellular part of Notch-1, Notch-1-IC, translocates into the nucleus, where it targets the DNA binding protein RBP-J kappa/CBF1. RBP-J kappa mediates repression ... through recruitment of a histone deacetylase-containing complex. The Notch-1-IC/RBP-J kappa complex overcomes repression and activates the transcription of Notch target genes. We have identified a novel domain in Notch-1-IC, the EP domain, which is indispensable for full transcriptional activation. This transactivation domain is localized adjacent to the ankyrin repeats of Notch-1-IC. In cotransfection experiments, Notch-1-IC-mediated transcriptional activation was inhibited by E1A12S and p53, two proteins, which interfere with the function of the common coactivator p300. Protein-protein interaction assays demonstrated the association of Notch-1-IC and the CH3 region of p300. In addition, the interaction of mammalian Notch-1-IC with p300 was destabilized after deletion of the EP domain of Notch-1-IC. Based on physical interaction with Notch-1-IC and coactivator functions of p300, we propose a model for Notch-1-mediated gene regulation via p300.
Mesh Terms:
Adenovirus E1A Proteins, Amino Acid Sequence, Animals, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, Cell Line, DNA-Binding Proteins, E1A-Associated p300 Protein, Electrophoretic Mobility Shift Assay, Green Fluorescent Proteins, Hela Cells, Homeodomain Proteins, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Luminescent Proteins, Mammals, Membrane Proteins, Mice, Molecular Sequence Data, Mutagenesis, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, Receptor, Notch1, Receptors, Cell Surface, Recombinant Fusion Proteins, Subcellular Fractions, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Tumor Suppressor Protein p53
Adenovirus E1A Proteins, Amino Acid Sequence, Animals, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, Cell Line, DNA-Binding Proteins, E1A-Associated p300 Protein, Electrophoretic Mobility Shift Assay, Green Fluorescent Proteins, Hela Cells, Homeodomain Proteins, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Luminescent Proteins, Mammals, Membrane Proteins, Mice, Molecular Sequence Data, Mutagenesis, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, Receptor, Notch1, Receptors, Cell Surface, Recombinant Fusion Proteins, Subcellular Fractions, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Tumor Suppressor Protein p53
Mol. Cell. Biol.
Date: Nov. 01, 2001
PubMed ID: 11604511
View in: Pubmed Google Scholar
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