Sp1 transcription factor as a target for anthracyclines: Effects on gene transcription

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• 作者：Sylvia Mansilla ; José ; Portugal
• 关键词：Sp1– ; DNA interactions ; Daunorubicin ; WP631 ; Transcription ; Jurkat T lymphocytes
• 刊名：Biochimie
• 出版年：2008
• 出版时间：July 2008
• 年：2008
• 卷：90
• 期：7
• 页码：976-987
• 全文大小：904 K

文摘

The analysis of how anthracyclines interfere with DNA–protein complexes, and the evaluation of their effects on gene transcription, can promote the development of new more specific anti-tumour agents. Daunorubicin and the bisintercalating anthracycline WP631 (which binds more tightly to DNA) have been compared for their ability to inhibit Sp1–DNA interactions and gene transcription. WP631 is more efficient at inhibiting transcription initiation from promoters containing an Sp1-binding site, and it is a potent inhibitor of Sp1-activated transcription both in vitro and in human cell lines. The analysis of gene expression profiles using arrays, which include several genes containing Sp1-putative binding sites, suggests that changes in the transcriptome induce cell cycle arrest and drive a time-dependent response of cells to death stimuli through distinct pathways, which rely on the anthracycline used and its concentration.