Convergence of b-catenin signaling and SF-1 Transcription Factor on StarD7 gene promoter

RENA VC; FLORES MARTIN J; ANGELETTI SOFÍA; PANZETTA DUTARI G; GENTI RAIMONDI S

Santiago de Chile

Congreso; IFPA (Internacional Federation of Placenta Associations) Meeting 2010; 2010

IFPA (Internacional Federation of Placenta Associations)

StarD7 belongs to the START-domain proteins that are involved in intracellular transport and lipid metabolism. StarD7 was first identified over-expressed in JEG-3 cells compared to normal and benign trophoblastic samples. We previously reported that StarD7 expression was independently regulated by β-catenin signaling and SF-1 factor at the transcriptional level. Herein, a possible convergence between both activating factors was investigated. To evaluate this hypothesis, JEG-3 cells were co-transfected with the SF-1 or/and the constitutively active β-catenin S33Y expression plasmids together with the -938/+157 StarD7 promoter construct, which contains the consensus binding sites recognized by both proteins. In addition, co-transfection assays were performed using these protein expression plasmids and mutated promoter versions in the SF-1 and TCF consensus sites (-938/+157 mut SF1-1 and -938/+157mut SF1-1/mut TCF). The results of this work show that SF-1 and β-catenin synergistically activate StarD7 promoter. Moreover, these findings indicate that TCF site localized at -614/-608 bp plays an important role in this activation. Furthermore, deletion of the 235-238 amino acid in the SF-1 transcription factor, involved in the β-catenin physical interaction, abolished this transcriptional activation; demonstrating that the interaction between the two proteins is necessary for an efficient StarD7 transcriptional activation. Finally, these data suggest that β-catenin could function as a bridge between SF-1 and TCF forming a ternary complex, which would transcriptionally activate StarD7 gene.