Transcriptional control of human CD2AP expression: the role of Sp1 and Sp3.

The CD2 associated protein (CD2AP) is characterized as a T-lymphocyte CD2 adapter protein and is found to be related to glomerulosclerosis, and CD2AP knockout mice develop a rapid onset nephrotic syndrome and die of renal failure. Here we report that the transcription factor Sp1 and Sp3 up-regulate the basal transcriptional activity of CD2AP and increase CD2AP expression at mRNA level. We show by Chromatin immunoprecipitation (ChIP) assay that Sp1 and Sp3 interact with the CD2AP promoter region in vivo. By transient transfection analysis we also demonstrate the mutations of Sp1/3 binding sites result in a profound reduction of CD2AP promoter activity. Overexpression of Sp1 and Sp3 transactivates the CD2AP promoter, whereas small interfering RNA-mediated (siRNA) blockage of Sp1 and Sp3 genes expressions inhibits markedly its activity. These results suggest that Sp1 and Sp3 play an important role in regulating CD2AP transcription through binding to the Sp1/3 binding sites.