DNA topoisomerase II poison TAS-103 transactivates GC-box-dependent transcription via acetylation of Sp1.
Drug-induced modifications of transcription factors play important roles in both apoptosis and survival signaling. The data presented here show that the DNA topoisomerase II poison TAS-103 transactivated the SV40 promoter in a GC-box-dependent manner and induced Sp1 acetylation in cells expressing p300. This activity was not observed in cells lacking p300. TAS-103 treatment also enhanced the p300 content of the nucleus and the interaction of p300 with Sp1. Cellular susceptibility to TAS-103 was correlated with p300 expression but not with topoisomerase II expression. Furthermore, the presence of p300 significantly sensitized cancer cells to TAS-103 but not to cisplatin. Taken together, these findings demonstrate novel genomic responses to anticancer agents that modulate Sp1 acetylation and Sp1-dependent transcription in an apoptotic pathway.
Torigoe
Takayuki
T
Department of Molecular Biology, University of Occupational and Environmental Health, School of Medicine, Fukuka, Japan.
Izumi
Hiroto
H
Wakasugi
Tetsuro
T
Niina
Ichiro
I
Igarashi
Tomonori
T
Yoshida
Takeshi
T
Shibuya
Izumi
I
Chijiiwa
Kazuo
K
Matsuo
Ken-ichi
K
Itoh
Hideaki
H
Kohno
Kimitoshi
K
D000107:Acetylation / Q000187:drug effects; D000634:Aminoquinolines / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D020862:GC Rich Sequence / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020218:Response Elements / Q000235:genetics*; D013539:Simian virus 40 / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D059005:Topoisomerase II Inhibitors; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation / Q000187:drug effects*
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D007192:Indenes; D009687:Nuclear Proteins; D016329:Sp1 Transcription Factor; D059005:Topoisomerase II Inhibitors; D015534:Trans-Activators; D004250:DNA Topoisomerases, Type II; C106647:6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one