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PMID: 11604511 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

p300 acts as a transcriptional coactivator for mammalian Notch-1.

Molecular and cellular biology ·Vol. 21 ·No. 22 ·2001-11-00 ·Pages 7761-74

Oswald F, Täuber B, Dobner T, Bourteele S, Kostezka U, Adler G, Liptay S, Schmid RM

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.

MeSH Terms
Adenovirus E1A Proteins/metabolism Amino Acid Sequence Animals Basic Helix-Loop-Helix Transcription Factors Binding Sites Cell Line DNA-Binding Proteins/metabolism E1A-Associated p300 Protein Electrophoretic Mobility Shift Assay Green Fluorescent Proteins HeLa Cells Homeodomain Proteins/genetics Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein Luminescent Proteins/genetics,metabolism Mammals Membrane Proteins/genetics,metabolism Mice Molecular Sequence Data Mutagenesis Nuclear Proteins/metabolism Promoter Regions, Genetic Protein Binding Receptor, Notch1 Receptors, Cell Surface Recombinant Fusion Proteins/genetics,metabolism Subcellular Fractions Trans-Activators/metabolism Transcription Factor HES-1 Transcription Factors Transcription, Genetic Transcriptional Activation Tumor Suppressor Protein p53/metabolism
Chemicals
Adenovirus E1A Proteins Basic Helix-Loop-Helix Transcription Factors DNA-Binding Proteins Hes1 protein, mouse Homeodomain Proteins Immunoglobulin J Recombination Signal Sequence-Binding Protein Luminescent Proteins Membrane Proteins NOTCH1 protein, human Notch1 protein, mouse Nuclear Proteins RBPJ protein, human Rbpj protein, mouse Receptor, Notch1 Receptors, Cell Surface Recombinant Fusion Proteins Trans-Activators Transcription Factor HES-1 Transcription Factors Tumor Suppressor Protein p53 Green Fluorescent Proteins HES1 protein, human E1A-Associated p300 Protein Ep300 protein, mouse
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Oswald F
Department of Internal Medicine, University of Ulm, Germany.
Täuber B
Dobner T
Bourteele S
Kostezka U
Adler G
Liptay S
Schmid R M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.22.7761-7774.2001
Published
2001-11-00
Pages
7761-74
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC99946
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.21.22.7761-7774.2001 PMC Full Text View journal details
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