Nuclear Factor-Y Binding to the Topoisomerase IIα Promoter Is Inhibited by Both the p53 Tumor Suppressor and Anticancer Drugs

2003 ◽  
Vol 63 (2) ◽  
pp. 359-367 ◽  
Author(s):  
Ashish A. Joshi ◽  
Zhong Wu ◽  
Robin F. Reed ◽  
D. Parker Suttle
Keyword(s):  
Tumor Suppressor ◽  
Anticancer Drugs ◽  
Nuclear Factor ◽  
Topoisomerase Iiα ◽  
P53 Tumor Suppressor ◽  
Nuclear Factor Y

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

2003 ◽  
Vol 374 (3) ◽  
pp. 723-729 ◽  
Author(s):  
Natisha MAGAN ◽  
Agnieszka P. SZREMSKA ◽  
Richard J. ISAACS ◽  
Kathryn M. STOWELL
Keyword(s):  
Transcription Factors ◽  
Functional Significance ◽  
Regulatory Elements ◽  
Resistant Cell ◽  
Nuclear Factor ◽  
Drug Resistant ◽  
Topoisomerase Iiα ◽  
Nuclear Factor Y ◽  
Specificity Protein ◽  
Drug Resistant Cell

topo IIα (topoisomerase IIα) 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 IIα 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 IIα 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 IIα 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.

Targeting the p53 tumor suppressor activity in glioblastomas using small molecule MDM2-inhibitor

2011 ◽  
Vol 42 (01) ◽  
Author(s):  
P. Monfared ◽  
T. Viel ◽  
G. Schneider ◽  
Y. Waerzeggers ◽  
S. Rapic ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Small Molecule ◽  
Suppressor Activity ◽  
P53 Tumor Suppressor ◽  
Tumor Suppressor Activity ◽  
Mdm2 Inhibitor
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