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Title 

Inhibition of protein phosphatases activates P4 promoter of the human insulin-like growth factor II gene through the specific promoter element

Authors 

Sang Won HyunKeunchil ParkYoung Sok LeeYoung Ik LeeSeong-Jin Kim

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

1994

Citation 

Journal of Biological Chemistry, vol. 269, no. 1, pp. 364-368

Keywords 

phosphoprotein phosphatasetranscription factorenzyme inhibitiongene expressionhuman cellpromoter regionprotein processingreceptor geneDNA-Binding Proteins

Abstract 

To understand the transcriptional regulation of the human insulin-like growth factor II (IGF-II) gene, we examined the effects of okadaic acid, a potent in vitro inhibitor of protein phosphatases, on the activation of human IGF-II gene expression. Treatment of A-549 human lung adenocarcinoma cells with okadaic acid increased expression of the IGF-II mRNAs. Since the 4.8-kb mRNA is transcribed under the control of human IGF-II P4 promoter, we examined the P4 promoter element responsible for the okadaic acid-mediated transcriptional activation. Transfection of IGF-II P4 promoter- chloramphenicol acetyltransferase constructs demonstrated that the effects of okadaic acid on the induction of IGF-II gene expression are mediated through multiple promoter elements, including an Egr-1 consensus element. We have also shown that okadaic acid induced the expression of the transcription factor Egr-1. Moreover, by using a GAL4-Egr-1 fusion protein, we have directly demonstrated that okadaic acid positively regulates Egr-1 transcriptional activity in vivo. These results indicate that protein phosphatases play an important role in the transcriptional regulation of the IGF-II.

ISSN 

0021-9258

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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