Transcriptional regulation of human placental leucine aminopeptidase/oxytocinase gene

被引:16
作者
Ito, T
Nomura, S [1 ]
Okada, M
Katsumata, Y
Iwase, A
Kikkawa, F
Tsujimoto, M
Mizutani, S
机构
[1] Nagoya Univ, Sch Med, Dept Obstet & Gynecol, Nagoya, Aichi 4668550, Japan
[2] RIKEN, Inst Phys & Chem Res, Lab Cellular Biochem, Wako, Saitama 3510148, Japan
关键词
aminopeptidase; AP-2; oxytocinase; placenta; promoter;
D O I
10.1093/molehr/7.9.887
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Human placental leucine aminopeptidase (P-LAP) plays a major role in the clearance of oxytocin, which is a key hormone in regulating labour pain. To explore the transcriptional regulation of P-LAP gene expression in placenta, we performed systematic studies using human choriocarcinoma cells, BeWo and JEG-3, as a model of placental trophoblastic cells. Transient transfection and luciferase assays using various 5 ' -deleted P-LAP-luciferase constructs showed that the region from -297 to +49 of the transcription start site was responsible for promoter activity in these cells. Footprinting analysis with nuclear extracts from both cell lines demonstrated at least four sites for nucleoprotein interactions in this region (FP1 to FP4). Site-directed deletion of FP1-4 in luciferase assays indicated the significance of the FP3 region (-214 to -183) for high promoter activity in the cells. Electrophoretic mobility shift assays to identify the proteins interacting with DNA at FP3 revealed three retarded bands, one of which was generated by activator protein-2 (AP-2) binding. Our findings suggest that AP-2 may be one of the important factors regulating P-LAP gene expression in human placenta.
引用
收藏
页码:887 / 894
页数:8
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