hADA3 is required for p53 activity.
The tumor suppressor protein p53 is a transcription factor that is frequently mutated in human cancers. In response to DNA damage, p53 protein is stabilized and activated by post-translational modifications that enable it to induce either apoptosis or cell cycle arrest. Using a novel yeast p53 dissociator assay, we identify hADA3, a part of histone acetyltransferase complexes, as an important cofactor for p53 activity. p53 and hADA3 physically interact in human cells. This interaction is enhanced dramatically after DNA damage due to phosphorylation event(s) in the p53 N-terminus. Proper hADA3 function is essential for full transcriptional activity of p53 and p53-mediated apoptosis.
Wang
T
T
Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Kobayashi
T
T
Takimoto
R
R
Denes
A E
AE
Snyder
E L
EL
el-Deiry
W S
WS
Brachmann
R K
RK
D000123:Acetyltransferases / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D005434:Flow Cytometry; D015723:Gene Library; D017930:Genes, Reporter; D016158:Genes, p53 / Q000235:genetics; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
D000903:Antibiotics, Antineoplastic; D018076:DNA, Complementary; C083323:NGG1 protein, S cerevisiae; D016376:Oligonucleotides, Antisense; D029701:Saccharomyces cerevisiae Proteins; C444103:TADA3 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D004247:DNA; D000123:Acetyltransferases; D051548:Histone Acetyltransferases