Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation / drug effects
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Aminoquinolines / pharmacology*
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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DNA Topoisomerases, Type II / metabolism
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GC Rich Sequence / genetics*
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Genes, Reporter / genetics
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Humans
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Indenes / pharmacology*
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Nuclear Proteins / metabolism
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Promoter Regions, Genetic / genetics
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Protein Binding
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Response Elements / genetics*
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Simian virus 40 / genetics
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Sp1 Transcription Factor / metabolism*
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Topoisomerase II Inhibitors*
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Trans-Activators / metabolism
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Transcription, Genetic / drug effects*
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Transcriptional Activation / drug effects*
Substances
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Aminoquinolines
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Antineoplastic Agents
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Indenes
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Nuclear Proteins
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Sp1 Transcription Factor
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Topoisomerase II Inhibitors
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Trans-Activators
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DNA Topoisomerases, Type II
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6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one