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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.
Biochem J. 2003 Sep 15; 374(Pt 3):723-9.BJ

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 to be transcriptional modulators with activator or repressor functions depending on protein/DNA context. Moreover, a functional interaction between Sp1 and NF-Y bound at proximal elements was observed.

Authors+Show Affiliations

Institute of Molecular BioSciences, Massey University, Private Bag 11-222, Palmerston North, New Zealand.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12769819

Citation

Magan, Natisha, et al. "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, vol. 374, no. Pt 3, 2003, pp. 723-9.
Magan N, Szremska AP, Isaacs RJ, et al. 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. Biochem J. 2003;374(Pt 3):723-9.
Magan, N., Szremska, A. P., Isaacs, R. J., & Stowell, K. M. (2003). 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, 374(Pt 3), 723-9.
Magan N, et al. 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. Biochem J. 2003 Sep 15;374(Pt 3):723-9. PubMed PMID: 12769819.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Magan,Natisha, AU - Szremska,Agnieszka P, AU - Isaacs,Richard J, AU - Stowell,Kathryn M, PY - 2003/05/27/accepted PY - 2003/05/12/revised PY - 2003/01/03/received PY - 2003/5/29/pubmed PY - 2003/10/1/medline PY - 2003/5/29/entrez SP - 723 EP - 9 JF - The Biochemical journal JO - Biochem J VL - 374 IS - Pt 3 N2 - 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 to be transcriptional modulators with activator or repressor functions depending on protein/DNA context. Moreover, a functional interaction between Sp1 and NF-Y bound at proximal elements was observed. SN - 1470-8728 UR - https://www.unboundmedicine.com/medline/citation/12769819/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_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20030032 DB - PRIME DP - Unbound Medicine ER -