CREB and Sp1 regulate the human CD2AP gene promoter activity in renal tubular epithelial cells.
The human CD2-associated protein (CD2AP) is involved in several molecular signaling pathways and is an important factor responsible for nephrotic syndrome. Here we report the identification of the transcription start point and promoter region of the human CD2AP gene in renal tubular epithelial cells. With luciferase assays and deletion analysis, we found that the region between -558 and -1bp ahead of the transcription start point is indispensable for the promoter activity of the human CD2AP gene. A CREB site and two Sp1 sites were essential for maintaining the basal transcriptional activity of the human CD2AP promoter. Overexpression of phosphorylated CREB and Sp1 transactivated the human CD2AP promoter, whereas small interfering RNA-mediated blockage of CREB and Sp1 genes expressions inhibited markedly its activity. These findings provide the first analysis of the human CD2AP gene promoter and demonstrate that not only CREB but also Sp1 plays a critical role in regulating basal CD2AP promoter activity in renal tubular epithelial cells.
Lu
Chao
C
Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, People's Republic of China.
Ren
Wei
W
Su
Xing-Ming
XM
Chen
Jie-Qing
JQ
Wu
Sheng-Hua
SH
Guo
Xi-Rong
XR
Huang
Song-Ming
SM
Chen
Long-Hua
LH
Zhou
Guo-Ping
GP
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D017362:Cyclic AMP Response Element-Binding Protein; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor