Oswald, Franz and Taeuber, Birgit and Dobner, Thomas and Bourteele, Soizic and Kostezka, Ulrike and Adler, Guido and Liptay, Susanne and Schmid, Roland M. (2001) p300 acts as a transcriptional coactivator for mammalian Notch-1. MOLECULAR AND CELLULAR BIOLOGY, 21 (22). pp. 7761-7774. ISSN 0270-7306, 1098-5549
Full text not available from this repository. (Request a copy)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-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RBP-J-KAPPA; SPLIT COMPLEX GENES; NEOPLASTIC TRANSFORMATION; INTRACELLULAR DOMAIN; MOUSE NOTCH1; NUCLEAR-LOCALIZATION; ANKYRIN REPEATS; CELL FATE; ACTIVATION; BINDING; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Nov 2021 13:10 |
| Last Modified: | 30 Nov 2021 13:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40985 |
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