Tip60 histone acetyltransferase acts as a negative regulator of Notch1 signaling by means of acetylation.
The Notch signaling pathway appears to perform an important function in a wide variety of organisms and cell types. In our present study, we provide evidence that UV irradiation-induced Tip60 proteins reduced Notch1 activity to a marked degree. Accumulated UV irradiation-induced Tip60 suppresses Notch1 transcriptional activity via the dissociation of ... the Notch1-IC-CSL complex. The binding between endogenous Tip60 and Notch1-IC in UV radiation-exposed cells was verified in this study by coimmunoprecipitation. Interestingly, the physical interaction of Tip60 with Notch1-IC occurs to a more profound degree in the presence of CSL but does not exist in a trimeric complex. Using Notch1-IC and Tip60 deletion mutants, we also determined that the N terminus, which harbors the RAM domain and seven ankyrin repeats of Notch1-IC, interacts with the zinc finger and acetyl coenzyme A domains of Tip60. Furthermore, here we report that Notch1-IC is a direct target of the acetyltransferase activity of Tip60. Collectively, our data suggest that Tip60 is an inhibitor of the Notch1 signaling pathway and that Tip60-dependent acetylation of Notch1-IC may be relevant to the mechanism by which Tip60 suppresses Notch1 signaling.
Mesh Terms:
Acetylation, Animals, Cell Line, Escherichia coli, Gene Deletion, Genes, Reporter, Glutathione Transferase, Histone Acetyltransferases, Humans, Kidney, Luciferases, Mice, Models, Biological, NIH 3T3 Cells, Precipitin Tests, Protein Structure, Tertiary, Receptor, Notch1, Recombinant Proteins, Signal Transduction, Ultraviolet Rays
Acetylation, Animals, Cell Line, Escherichia coli, Gene Deletion, Genes, Reporter, Glutathione Transferase, Histone Acetyltransferases, Humans, Kidney, Luciferases, Mice, Models, Biological, NIH 3T3 Cells, Precipitin Tests, Protein Structure, Tertiary, Receptor, Notch1, Recombinant Proteins, Signal Transduction, Ultraviolet Rays
Mol. Cell. Biol.
Date: Sep. 01, 2007
PubMed ID: 17636029
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