Acetylation status of E2F-1 has an important role in the regulation of E2F-1-mediated transactivation of tumor suppressor p73.
Tumor suppressor p73 plays an important role in the regulation of DNA damage response. E2F-1 acts as a transcriptional regulator for p73. In the present study, we have found that acetylation of E2F-1 has a critical role in the E2F-1-mediated transactivation of p73. In response to adriamycin (ADR), p73 was stabilized in HeLa cells and the expression levels of its target genes increased in association with an induction of apoptosis. Of note, E2F-1 and several its target genes were transactivated in response to ADR, whereas p73 mRNA level remained unchanged. Immunoprecipitation analysis revealed that ADR has a marginal effect on acetylation status of E2F-1. Intriguingly, acetylation level of E2F-1 remarkably increased in the presence of trichostatin A (TSA) and thereby inducing the expression level of p73 mRNA. Taken together, our present findings suggest that acetylation status of E2F-1 contributes to the selective activation of its target genes.
Ozaki
Toshinori
T
Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan. tozaki@chiba-cc.jp
Okoshi
Rintaro
R
Sang
Meixiang
M
Kubo
Natsumi
N
Nakagawara
Akira
A
D000107:Acetylation / Q000187:drug effects; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004317:Doxorubicin / Q000494:pharmacology; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D015533:Transcriptional Activation; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000903:Antibiotics, Antineoplastic; D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D004317:Doxorubicin