Identification of c-myc as a down-stream target for pituitary tumor-transforming gene.

Pituitary tumor-transforming gene (PTTG) encodes a protein implicated in cellular transformation and transcriptional regulation. To identify downstream target genes, I established cell lines with tightly regulated inducible expression of PTTG. DNA arrays were used to analyze gene expression profiles after PTTG induction. I identified c-myc oncogene as a major PTTG target. Induction of PTTG resulted in increased cell proliferation through activation of c-myc. I showed that PTTG activates c-myc transcription in transfected cells. PTTG binds to c-myc promoter near the transcription initiation site in a protein complex containing the upstream stimulatory factor (USF1). I have defined the PTTG DNA-binding site and mapped PTTG DNA binding domain to a region between amino acids 61 and 118. Furthermore, I demonstrated that PTTG DNA binding is required for its transcriptional activation function. These results definitively established the role of PTTG as a transcription activator and indicate that PTTG is involved in cellular transformation and tumorigenesis through activation of c-myc oncogene.