All-trans retinoic acid up-regulates the human CD2AP gene expression through Sp1/Sp3 binding sites

All-trans retinoic acid (ATRA), an active metabolite of vitamin A, plays an important role in regulating cell differentiation, proliferation, and apoptosis. It was reported that ATRA could cause an up-regulation of protein expression of CD2AP in nephrotic animals. However, the mechanism of ATRA-mediated up-regulation is not well understood. In the present study, deletion analysis and luciferase assays demonstrated that ATRA caused a marked increase in the activity of the CD2AP promoter, and the region between nt -599 and -328 from the transcription start site, where there are two clusters of Sp1/3 binding sites, was indispensable for ATRA-mediated up-regulation. Chromatin immunoprecipitation assays revealed that ATRA activated the CD2AP transcription through enhancing the DNA-binding activity of Sp1 and Sp3 with the CD2AP promoter. Taken together, this study provided evidence for the first time showing the stimulating effect of ATRA on CD2AP and new therapeutic strategies for the treatment of nephritic syndrome and other associated diseases of CD2AP deficiency.