p300 Acts as a Transcriptional Coactivator for Mammalian Notch-1
AUTOR(ES)
Oswald, Franz
FONTE
American Society for Microbiology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=99946Documentos Relacionados
- Regulation of β-catenin transformation by the p300 transcriptional coactivator
- Polyomavirus Large T Antigen Binds the Transcriptional Coactivator Protein p300
- Recruitment of p300 by C/EBPβ triggers phosphorylation of p300 and modulates coactivator activity
- p300 is a component of an estrogen receptor coactivator complex.
- HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator
