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.
Kim
Mi-Yeon
MY
Hormonre Research Center, School of Biological Sciences and Technology, Chonnam National University, Yongbong-dong, Buk-ku, Gwangju 500-757, South Korea.
Ann
Eun-Jung
EJ
Kim
Jin-Young
JY
Mo
Jung-Soon
JS
Park
Ji-Hye
JH
Kim
Sun-Yee
SY
Seo
Mi-Sun
MS
Park
Hee-Sae
HS
D000107:Acetylation; D000818:Animals; D002460:Cell Line; D004926:Escherichia coli / Q000235:genetics; D017353:Gene Deletion; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D007668:Kidney / Q000166:cytology; D008156:Luciferases / Q000378:metabolism; D000074443:Lysine Acetyltransferase 5; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators; D014466:Ultraviolet Rays
C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011994:Recombinant Proteins; D015534:Trans-Activators; D008156:Luciferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; C523065:Kat5 protein, mouse; D000074443:Lysine Acetyltransferase 5; D005982:Glutathione Transferase