scholarly journals Measurement of the binding of transcription factor Sp1 to a single GC box recognition sequence

1989 ◽  
Vol 17 (7) ◽  
pp. 2639-2653 ◽  
Author(s):  
John Letovsky ◽  
William S. Dynan
2007 ◽  
Vol 292 (5) ◽  
pp. G1221-G1227 ◽  
Author(s):  
Wensheng Chen ◽  
Shi-Ying Cai ◽  
Shuhua Xu ◽  
Lee A. Denson ◽  
Carol J. Soroka ◽  
...  

Multidrug resistance-associated protein MRP3/Mrp3 (ABCC3) is upregulated in cholestasis, an adaptive response that may protect the liver from accumulation of toxic compounds, such as bile salts and bilirubin conjugates. However, the mechanism of this upregulation is poorly understood. We and others have previously reported that fetoprotein transcription factor/liver receptor homolog-1 is an activator of MRP3/Mrp3 expression. In searching for additional regulatory elements in the human MRP3 promoter, we have now identified nuclear receptor retinoic X receptor-α:retinoic acid receptor-α (RXRα:RARα) as a repressor of MRP3 activation by transcription factor Sp1. A luciferase reporter assay demonstrated that cotransfection of transcription factor Sp1 stimulates the MRP3 promoter activity and that additions of RXRα:RARα abrogated this activation in a dose-dependent manner. Site mutations and gel shift assays have identified a Sp1 binding GC box motif at −113 to −108 nts upstream from the MRP3 translation start site, where RXRα:RARα specifically reduced Sp1 binding to this site. Mutation of the GC box also reduced MRP3 promoter activity. The functional role of RXRα:RARα as a repressor of MRP3 expression was further confirmed by RARα small-interfering RNA knockdown in HepG2 cells, which upregulated endogenous MRP3 expression. In summary, our results indicate that activator Sp1 and repressor RXRα:RARα act in concert to regulate MRP3 expression. Since RXRα:RARα expression is diminished by cholestatic liver injury, loss of RXRα:RARα may lead to upregulation of MRP3/Mrp3 expression in these disorders.


1999 ◽  
Vol 31 (3) ◽  
pp. 217-229 ◽  
Author(s):  
Olivier Ramon ◽  
Sylvie Sauvaigo ◽  
Didier Gasparutto ◽  
Patrice Faure ◽  
Alain Favier ◽  
...  

1996 ◽  
Vol 16 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Michael C. MacLeod ◽  
K. Leslie Powell ◽  
Vladimir A. Kuzmin ◽  
Aleksandr Kolbanovskiy ◽  
Nicholas E. Geacintov

2000 ◽  
Vol 38 (2) ◽  
pp. 224-227 ◽  
Author(s):  
Pengfei GONG ◽  
Yasumitsu OGRA ◽  
Shinji KOIZUMI

Biochemistry ◽  
2004 ◽  
Vol 43 (51) ◽  
pp. 16027-16035 ◽  
Author(s):  
Shinichiro Oka ◽  
Yasuhisa Shiraishi ◽  
Takuya Yoshida ◽  
Tadayasu Ohkubo ◽  
Yukio Sugiura ◽  
...  

2021 ◽  
Vol 561 ◽  
pp. 172-179
Author(s):  
Yannan Zhao ◽  
Dingjin Yao ◽  
Yi Li ◽  
Si Zhang ◽  
Zhonghua Tao ◽  
...  

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