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p300 Acts as a Transcriptional Coactivator for Mammalian Notch-1

By Franz Oswald, Birgitt Täuber, Thomas Dobner, Soizic Bourteele, Ulrike Kostezka, Guido Adler, Susanne Liptay and Roland M. Schmid

Abstract

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-Jκ/CBF1. RBP-Jκ mediates repression through recruitment of a histone deacetylase-containing complex. The Notch-1-IC/RBP-Jκ 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

Topics: Transcriptional Regulation
Publisher: American Society for Microbiology
Year: 2001
DOI identifier: 10.1128/MCB.21.22.7761-7774.2001
OAI identifier: oai:pubmedcentral.nih.gov:99946
Provided by: PubMed Central
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