Modulation of DNA topoisomerase II alpha promoter activity by members of the Sp (specificity protein) and NF-Y (nuclear factor Y) families of transcription factors

The Biochemical Journal
Natisha MaganKathryn M Stowell

Abstract

Topo IIalpha (topoisomerase IIalpha) is a major target of several commonly used anticancer drugs and is subject to down-regulation at the transcriptional level in some drug-resistant cell lines and tumours in response to chemotherapy. Clinical resistance to such drugs has been correlated with down-regulation of topo IIalpha at transcription in some drug-resistant cell lines and tumours. Putative binding sites for a variety of transcription factors, including Sp1 (specificity protein 1) and NF-Y (nuclear factor Y) have previously been identified in the topo IIalpha promoter, but their functional significance and interactions have not been described following exposure to anti-cancer drugs. The binding of these factors to specific putative regulatory elements in the topo IIalpha promoter was studied using electrophoretic-mobility-shift assays. Sp1 was found to bind strongly to both distal and proximal GC-rich elements and NF-Y to ICB1 (the first inverted CCAAT box). The functional significance of transcription-factor binding was studied using transient transfection of HeLa cells using a luciferase reporter driven by a 617-bp minimal promoter containing point mutations in putative regulatory elements. Sp1 and NF-Y were both found t...Continue Reading

Citations

May 24, 2005·Matrix Biology : Journal of the International Society for Matrix Biology·David C ColterDavid G Stokes
Feb 19, 2009·Nucleic Acids Research·Michal StrosSárka Pospísilová
Aug 21, 2007·Anti-cancer Drugs·Lin WangLi-Jian Xian
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Nov 14, 2008·Journal of Dermatological Science·Shibo YingHidenari Takahara
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Nov 2, 2019·Genes·Joyce H Lee, James M Berger
Aug 17, 2021·Protein Science : a Publication of the Protein Society·Alexandre Duprey, Eduardo A Groisman

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