Pituitary tumor transforming gene (PTTG1) was isolated from rat pituitary tumor cells, and subsequently identified as a securin protein as well as a transcription factor. We test the a global transcriptional effect of PTTG1 in human choriocarcinoma JEG-3 cells by simultaneously assessing 20,000 gene promoters with ChIP-on-Chip and observed enrichment of 746 gene promoters (P<0.001). Significant interaction between PTTG1 and Sp1 (P<0.000001) was found by transcriptional pattern analysis of ChIP data and further confirmed by immunoprecipitaion and pull-down assays. PTTG1 acts coordinately with Sp1 to induce cyclin D3 expression ~3-fold, and promotes G1/S phase transition independently of p21. PTTG1 deletion was also protective for anchorage-independent cell colony formation. The results show that PTTG1 exhibits properties of a global transcription factor, and specifically modulates the G1/S phase transition by interacting with Sp1. In addtion to functioning as a securin, this novel signaling pathway may be required for PTTG1 transforming activity.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA